Experimental Hematology and Cancer Biology

Division Details

Division Data Summary

Research and Training Details

Number of Faculty24
Number of Joint Appointment Faculty14
Number of Research Fellows35
Number of Research Students17
Number of Support Personnel83
Direct Annual Grant Support$7,783,205
Direct Annual Industry Support$274,014
Peer Reviewed Publications75

Division Photo

Experimental Hematology and Cancer Biology

Row 1: MD Filippe, L Privette-Vinnedge

Row 2: T Kalfa, E Grassman, R Drissi, M Azam

Row 3: F Guo, J Wu, R Meetei, C Lutzko, R Waclaw, H Van der loo, J Mulloy

Row 4: P Andreassen, N Nassar, L Chow, D Reynaud, D Starczynowski, B DasGupta, Y Zheng

Row 5: M Flick, J Cancelas, Q Pang, J Degen, G Huang

Research Highlights

Yi Zheng, PhD

Rational design of small molecule inhibitors targeting Rho GTPase activation cascade. We reported in PNAS and Chemistry & Biology the rational design of a small-molecule inhibitor of the RhoA activator, LARG, that helped stop the spread of laboratory cultured human breast cancer cells, especially when it was used with another chemical inhibitor known as Rhosin/G04 which is specific toward RhoA itself. The studies provide novel therapeutic principle for rational drug design and discovery.

Paul Andreassen, PhD

The Andreassen lab has recently demonstrated that the machinery for homologous recombination is linked to early events in DNA damage signaling by ubiquitin-dependent signaling and PALB2/FANCN. We have also generated novel insight into the function of RAD51 paralogs in DNA repair by finding that RAD51C/FANCO interacts with PALB2/FANCN.

Jose Cancelas, MD, PhD

The Cancelas Lab has been working on the following studies:

  • Discovery and elucidation of the role of Vav3 in BCR-ABL lymphoblastic leukemia.
  • Identification of connexin43 (Cx43) as a regulator of reactive oxygen content (ROS) in hematopoietic stem cells and description of a novel protective function of bone marrow stroma consisting of scavenging of ROS through Cx43.
  • Elucidation of the role of Klf5 in stem cell adhesion and homing to the bone marrow with identification of Rab5 as the crucial downstream gene responsible for loss of integrin mediated cell adhesion in stem cells.
  • In vivo demonstration of the safety of platelet additive solution Isoplate to maintain platelet storage for up to five days in a multicenter trial.
  • In vivo demonstration of the ability of DMSO to freeze platelets and maintain their viability in a multicenter trial.

Jay Degen, PhD

The Degen Lab is genetically eliminating the fibrinogen binding motif recognized by the microglial integrin receptor CD11b/CD18;shown to inhibit perivascular microglial clustering and axonal damage within the central nervous system in a mouse model of multiple sclerosis.

In other work, the Degen Lab has shown thrombin-mediated proteolysis to be an unexpectedly powerful determinant of atherosclerosis in multiple distinct settings. These studies suggest that selective anticoagulants employed to prevent thrombotic events may also be remarkably effective in clinically impeding cardiovascular disease.

Finally, the Degen Lab has shown the host fibrin(ogen) and the S. aureus-encoded fibrinogen receptor, ClfA, to be dual determinants of bacterial virulence. These findings suggest that therapeutic interventions at the level of fibrinogen could be advantageous in S. aureus septicemia.

Matthew Flick, PhD

The Flick Lab has continued analysis of the pathogenesis of bacterial infection including a publication highlighting the mechanisms of microbe engagement of fibrinogen the pathogenesis of S. aureus septicemia.

In addition, the Flick Lab has initiated a new project, funded by an industry contract with Novo Nordisk, to study the efficacy of recombinant factor XIII in treating inflammatory arthritis.

Hartmut Geiger, PhD

The Geiger Lab published a paper in Nature Medicine on radiomitigation which received national attention.

Elke Grassman, PhD, HCLD

The Grassman Lab qualified four new specialized assays for patient monitoring for a thalassemia gene therapy trial.

The Grassman Lab published two papers in Gene Therapy. One was entitled, "Scale-up and manufacturing of clinical-grade self-inactivating gamma-retroviral vectors by transient transfection." The second paper was entitled, "Critical variables affecting clinical-grade production of the self-inactivating gamma-retroviral vector for the treatment of X-linked severe combined immunodeficiency."

Fukun Guo, PhD

The Guo Lab is studying the following:

  • The role of mTOR in hematopoiesis.
  • The role of Cdc42 in T cell activation.
  • The role of RhoA in T cell development and activation.
  • mTOR as a potential therapeutic target in T lymphocytic leukemia.

Carolyn Lutzko, PhD

The Lutzko Lab has developed specialized induced pluripotent stem cells from patients with blood diseases including neutropenia, sickle cell anemia and leukocyte adhesion deficiency. These specialized stem cells allow us to produce blood cells with the "disease" in the dish to directly develop and test gene, cell and drug therapies for these blood diseases.

Punam Malik, MD

The Malik Lab is working on:

  • A clinical trial for gene therapy for sickle cell disease.
  • Gene therapy for HLH with Drs. Jordan and Risma.
  • A clinical trial for sickle nephropathy.

Ruhikanta Meetei, PhD

The Meetei Lab has:

  • Discovered a 20kDa subunit of FA core complex protein and it was published in the journal Blood.
  • Identified an important site of phosphorylation (S1045) in FANCM protein in response to DNA damage. This was published in the Cancer Research journal.

James Mulloy, PhD

The Mulloy Lab has:

  • Defined the role that Thrombopoeitic/MPL/Bcl-xL plays downstream of the AML1-ETO oncogene.
  • Established a chemotherapy regimen for AML in immunodeficient mice.

Nicolas Nassar, PHD

The Nassar Lab is working on the following:

  • Rational design of a Vav/Rac inhibitor as a new therapy for high risk B-ALL.
  • A novel and rationally designed Ras inhibitors for high risk B-ALL Multi-target therapy.

Dao Pan, PhD

The Pan Lab has reported in PNAS the development of a recombinant receptor-binding domain (Rb) of ApoE that enables protein delivery across the blood-brain barrier in mice when being tagged with a lysosomal enzyme as a fusion protein. The studies provide a noninvasive and BBB-targeted procedure for delivery of large molecule therapeutic agents to treat diseases involving the brain.

The Pan lab has also conducted preclinical evaluation of the blood-brain-barrier targeted Rb they recently developed, and showed that long-term systemic delivery of BBB-targeted IDUA-Rb could achieve superb neurological benefits over control protein with complete normalization of behavioral deficits in high-dosage groups and partial correction of brain pathology in medium group. This study has been presented at the 16th Annual meeting of American Society of Cell and Gene Therapy, and Dr. Salim El-Amouri from the lab received a 2013 ASGCT Travel Award.

The Pan lab has recently demonstrated for the first time that megakaryocytes/platelets are capable of over-producing, packaging and storing a lysosomal enzyme which retains proper catalytic activity, lysosomal enzyme trafficking and endogenous M6PR-mediated uptake, as well as the ability of cross-correction in patient’s cells. This study has been presented at the 2012 ASH meeting in December, and Dr. Mei Dai from the lab received ASH Abstract Achievement Award.

The Pan lab has recently demonstrated that long-term visceral phenotypic corrections could be further improved by stress erythropoiesis with complete normalization in spleen of MPS I mice with minimum HSC gene transfer (<1%) after lentiviral vector-mediated hematopoietic stem cell gene therapy using a erythroid/megakaryocytic promoter. These studies provide valuable preclinical information that may lead to future clinical trial. This study has been presented at the 16th Annual meeting of American Society of Cell and Gene Therapy, and Dr. Jing-fen Han, from the lab, has received a 2013 ASGCT Travel Award.

Qishen Pang, PhD

The study, “Link between abnormal HSC differentiation and disease progression in FA”, shows that FA deficiency enhances Notch signaling in multipotential progenitors (MPPs), which is correlated with decreased phenotypic long-term HSCs and increased formation of MPP1 progenitors. The findings have implications for understanding the pathogenesis of BM failure and leukemia in FA, and suggest possible translational approaches to these devastating clinical complications. A manuscript describing these studies is in press in J. Immunology.

In addition, the study, “Targeting the FA pathway in sensitizing leukemia to chemotherapy”, demonstrates that the mTOR kinase inhibitor pp242 enhances anti-tumor activity of conventional chemo-drugs in vitro and in vivo by suppressing FANCD2 and consequently augmenting DNA damage leading to apoptosis. The finding suggests that inhibition of the FA pathway coupled with chemo-therapy may be beneficial for cancer treatment. A manuscript describing these studies is in press in Leukemia.

Nancy Ratner, PhD

The Ratner Lab has published a paper in the Journal of Neuroscience showing that Rac1 controls Schwann cell myelination through cAMP and NF2/merlin.  A critical role for cAMP downstream of the small GTPase Rac1 had not previously been defined in vivo.

The Ratner Lab published a paper showing Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition Acta Neuropathol. This shows for the first time that macrophages comprise 30% of cells in neurofibromas.

The Ratner Lab published a paper in The Journal of Clinical Investigation that shows MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors. This paper shows that MEK inhibition shrinks most neurofibromas in an accurate mouse model of NF1 disease. The paper received considerable PR and two ongoing clinical trials have resulted from this work.

The Ratner Lab published a paper in Cancer Research that shows nPTEN and NF1 inactivation in Schwann cells produce a severe phenotype in the peripheral nervous system that promotes the development and malignant progression of peripheral nerve sheath tumors.

The Ratner Lab published a paper in Sarcoma showing then conditional Inactivation of Pten with EGFR Overexpression in Schwann Cells Models Sporadic MPNST.

The Ratner Lab published a paper in Nature Genetics showing the forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis. This is an important paper identifying novel potential driver mutations in MPNST, an incurable human sarcoma.

The Ratner Lab published a paper in Cancer Discover showing the Canonical Wnt/beta-catenin Signaling Drives Human Schwann Cell Transformation, Progression, and Tumor Maintenance. This is a paper identifying multiple modes for activating b-catenin signaling MPNST, an incurable human sarcoma.

The Ratner Lab published a paper in Oncogen showing EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors.

Damien Reynaud, PhD

The Reynaud laboratory was set up in March 2013 with the purchase of essential equipment. Recruitment and training of lab personnel (one research assistant and one postdoctoral fellow) has been initiated. The first set of experiments describing the hematopoietic compartments present in the neonate bone marrow have been performed.

Daniel Starczynowski, PhD

The Starczynowski Lab was awarded a Gabrielle’s Angels Foundation Research Award.

The Starczynowski Lab published “Cytotoxic effects of Bortezomib in MDS/AML depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1” in Blood (July 2012).

Johannes van der Loo, BA, MS, PhD

The van der Loo Lab published a paper describing the development and scale-up for manufacturing of clinical-grade gamma-retroviral vectors in a bioreactor. The paper was published in the journal Gene Therapy.

The van der Loo Lab published a paper on the critical variables evaluated during the clinical-grade production of a self-inactivating gamma-retroviral vector for the treatment of X-linked severe combined immunodeficiency in an international multi-institutional phase I trial. The product is currently being used in London, Paris, Los Angeles, Boston and Cincinnati. The paper was published in the journal Gene Therapy.

The van der Loo Lab completed clinical manufacturing of three (3) lots of GMP-grade lentiviral vector for the treatment of Sickle Cell Anemia for a phase I trial to be opened at Cincinnati Children’s (PI: Malik).

Ronald Waclaw, PhD

The Waclaw Lab is analyzing the role of the RASopathy gene, Shp2 (PTPN11) during mouse brain development. We have found that loss of Shp2 and misexpression of a Noonan Syndrome GOF mutation impacts the normal generation and differentiation of oligodendrocytes in the telencephalon. We are currently writing this manuscript for submission.

The Waclaw Lab is analyzing the role of the RASopathy gene, NF1 (neurofibromin) during mouse basal ganglia development. We have found that loss of NF1 impacts both the striatal differentiation and normal formation of striatal circuitry. We are currently writing a manuscript for submission.

Additionally, the Waclaw Lab is analyzing mouse models of glioma at "pre tumor" stages to determine the role of early developmental genes at early stages of gliomagenesis. We have identified several candidate genes normally expressed in progenitor niches of the telencephalon and are now characterizing several defined signaling pathways in combination with these factors.

Jianqiang Wu, MD, MS

The Wu Lab is studying the following: Stat3 in neurofibroma initiation and maintenance. miR-155 and RUNX function in neurofibroma formation and therapy.

Significant Publications

Chang, K.H., A. Sanchez-Aguilera, S. Shen, A. Sengupta, M.N. Madhu, A.M. Ficker, S.K. Dunn, A.M. Kuenzi, J.L. Arnett, R.A. Santho, X. Agirre, J.P. Perentesis, M.W. Deininger, Y. Zheng, X.R. Bustelo, D.A. Williams, and J.A. CancelasVav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival. Blood. 2012. 120:800-811.
Despite the introduction of tyrosine kinase inhibitor therapy, the prognosis for p190-BCR-ABL(+) acute lymphoblastic leukemia remains poor. This paper defines the cellular and molecular roles of the Rho GTPase guanine nucleotide exchange factor Vav in lymphoid leukemogenesis and explore the roles of Vav proteins in BCR-ABL-dependent signaling.  The study concludes that Vav3 represents a novel specific molecular leukemic effector for multitarget therapy in p190-BCR-ABL-expressing acute lymphoblastic leukemia.
Chou, F.S., A. Griesinger, M. Wunderlich, S. Lin, K.A. Link, M. Shrestha, S. Goyama, B. Mizukawa, S. Shen, G. Marcucci, and J.C. MulloyThe thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO. Blood. 2012. 120:709-719.
AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. This report shows that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO-induced MPL.
Fang, J., G. Rhyasen, L. Bolanos, C. Rasch, M. Varney, M. Wunderlich, S. Goyama, G. Jansen, J. Cloos, C. Rigolino, A. Cortelezzi, J.C. Mulloy, E.N. Oliva, M. Cuzzola, and D.T. Starczynowski. Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1. Blood. 2012. 120:858-867.
Bortezomib (Velcade) is used widely for the treatment of various human cancers; however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. This work find that bortezomib induces proteasome-independent degradation of the TRAF6 protein, but not mRNA, in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cell lines and primary cells. The studies present novel mechanisms by which TRAF6 is regulated through bortezomib/autophagy-mediated degradation and by which it alters MDS/AML sensitivity to bortezomib by controlling PSMA1 expression.
Flick, M.J., X. Du, J.M. Prasad, H. Raghu, J.S. Palumbo, E. Smeds, M. Hook, and J.L. Degen. Genetic elimination of the binding motif on fibrinogen for the S. aureus virulence factor ClfA improves host survival in septicemia. Blood. 2013. 121:1783-1794.
Fibrinogen can support host antimicrobial containment/clearance mechanisms, yet selected pathogens appear to benefit from host procoagulants to drive bacterial virulence. This paper explored the hypothesis that host fibrin(ogen), on balance, supports Staphylococcus aureus infection in the context of septicemia. The findings indicate that host fibrin(ogen) and bacterial ClfA are dual determinants of virulence and that therapeutic interventions at the level of fibrinogen could be advantageous in S. aureus septicemia.
Patmore, D.M., S. Welch, P.C. Fulkerson, J. Wu, K. Choi, D. Eaves, J.J. Kordich, M.H. Collins, T.P. Cripe, andN. Ratner. In vivo regulation of TGF-beta by R-Ras2 revealed through loss of the RasGAP protein NF1. Cancer research. 2012. 72:5317-5327.
Ras superfamily proteins participate in TGF-β-mediated developmental pathways that promote either tumor suppression or progression. However, the specific Ras proteins, which integrate in vivo with TGF-β signaling pathways, are unknown. To resolve this question, the authors activated all Ras proteins in vivo by genetic deletion of the RasGAP protein Nf1 and examined mice doubly deficient in a Ras protein to determine its requirement in formation of TGF-β-dependent neurofibromas that arise in Nf1-deficient mice. The finding reveals R-Ras2 as a critical regulator of TGF-β signaling in vivo.

Division Publications

Experimental Hematology Publications

  1. Acosta MT, Bearden CE, Castellanos FX, Cutting L, Elgersma Y, Gioia G, Gutmann DH, Lee YS, Legius E, Muenke M, North K, Parada LF, Ratner N, Hunter-Schaedle K, Silva AJ. The Learning Disabilities Network (LeaDNet): using neurofibromatosis type 1 (NF1) as a paradigm for translational research. Am J Med Genet A. 2012; 158A:2225-32.
  2. Akunuru S, James Zhai Q, Zheng Y. Non-small cell lung cancer stem/progenitor cells are enriched in multiple distinct phenotypic subpopulations and exhibit plasticity. Cell Death Dis. 2012; 3:e352.
  3. Azam M. An in vitro screening to identify drug-resistant mutations for target-directed chemotherapeutic agents. In: y zheng, ed. Rational Drug Design - Methods Mol Biol. New York: Springer; 2012:175-84.
  4. Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I, Wang WC, Hoppe C, Hagar W, Darbari DS, Malik P. Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. ScientificWorldJournal. 2012; 2012:949535.
  5. Barger JF, Gallo CA, Tandon P, Liu H, Sullivan A, Grimes HL, Plas DR. S6K1 determines the metabolic requirements for BCR-ABL survival. Oncogene. 2013; 32:453-61.
  6. Bell-Horwath TR, Vadukoot AK, Thowfeik FS, Li G, Wunderlich M, Mulloy JC, Merino EJ. Novel ROS-activated agents utilize a tethered amine to selectively target acute myeloid leukemia. Bioorg Med Chem Lett. 2013; 23:2951-4.
  7. Borissoff JI, Otten JJ, Heeneman S, Leenders P, van Oerle R, Soehnlein O, Loubele ST, Hamulyák K, Hackeng TM, Daemen MJ, Degen JL, Weiler H, Esmon CT, van Ryn J, Biessen EA, Spronk HM, ten Cate H. Genetic and pharmacological modifications of thrombin formation in apolipoprotein e-deficient mice determine atherosclerosis severity and atherothrombosis onset in a neutrophil-dependent manner. PLoS One. 2013; 8:e55784.
  8. Chang KH, Sanchez-Aguilera A, Shen S, Sengupta A, Madhu MN, Ficker AM, Dunn SK, Kuenzi AM, Arnett JL, Santho RA, Agirre X, Perentesis JP, Deininger MW, Zheng Y, Bustelo XR, Williams DA, Cancelas JA. Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival. Blood. 2012; 120:800-11.
  9. Chapman H, Waclaw RR, Pei Z, Nakafuku M, Campbell K. The homeobox gene Gsx2 controls the timing of oligodendroglial fate specification in mouse lateral ganglionic eminence progenitors. Development. 2013; 140:2289-98.
  10. Chen L, Acciani T, Le Cras T, Lutzko C, Perl AK. Dynamic regulation of platelet-derived growth factor receptor alpha expression in alveolar fibroblasts during realveolarization. Am J Respir Cell Mol Biol. 2012; 47:517-27.
  11. Chen X, Skutt-Kakaria K, Davison J, Ou YL, Choi E, Malik P, Loeb K, Wood B, Georges G, Torok-Storb B, Paddison PJ. G9a/GLP-dependent histone H3K9me2 patterning during human hematopoietic stem cell lineage commitment. Genes Dev. 2012; 26:2499-511.
  12. Chou FS, Griesinger A, Wunderlich M, Lin S, Link KA, Shrestha M, Goyama S, Mizukawa B, Shen S, Marcucci G, Mulloy JC. The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO. Blood. 2012; 120:709-19.
  13. Davalos D, Ryu JK, Merlini M, Baeten KM, Le Moan N, Petersen MA, Deerinck TJ, Smirnoff DS, Bedard C, Hakozaki H, Gonias Murray S, Ling JB, Lassmann H, Degen JL, Ellisman MH, Akassoglou K. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat Commun. 2012; 3:1227.
  14. Delaney MK, Liu J, Zheng Y, Berndt MC, Du X. The role of Rac1 in glycoprotein Ib-IX-mediated signal transduction and integrin activation. Arterioscler Thromb Vasc Biol. 2012; 32:2761-8.
  15. Duan W, Gao L, Zhao W, Leon M, Sadee W, Webb A, Resnick K, Wu X, Ramaswamy B, Cohn DE, Shapiro C, Andreassen PR, Otterson GA, Villalona-Calero MA. Assessment of FANCD2 nuclear foci formation in paraffin-embedded tumors: a potential patient-enrichment strategy for treatment with DNA interstrand crosslinking agents. Transl Res. 2013; 161:156-64.
  16. Dumont LJ, Cancelas JA, Dumont DF, Siegel AH, Szczepiorkowski ZM, Rugg N, Pratt PG, Worsham DN, Hartman EL, Dunn SK, O'Leary M, Ransom JH, Michael RA, Macdonald VW. A randomized controlled trial evaluating recovery and survival of 6% dimethyl sulfoxide-frozen autologous platelets in healthy volunteers. Transfusion. 2013; 53:128-37.
  17. Dumont LJ, Cancelas JA, Graminske S, Friedman KD, Vassallo RR, Whitley PH, Rugg N, Dumont DF, Herschel L, Siegal AH, Szczepiorkowski ZM, Fender L, Razatos A. In vitro and in vivo quality of leukoreduced apheresis platelets stored in a new platelet additive solution. Transfusion. 2013; 53:972-80.
  18. El-Amouri SS, Cao P, Miao C, Pan D. Secreted luciferase for in vivo evaluation of systemic protein delivery in mice. Mol Biotechnol. 2013; 53:63-73.
  19. Fang J, Rhyasen G, Bolanos L, Rasch C, Varney M, Wunderlich M, Goyama S, Jansen G, Cloos J, Rigolino C, Cortelezzi A, Mulloy JC, Oliva EN, Cuzzola M, Starczynowski DT. Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1. Blood. 2012; 120:858-67.
  20. Flick MJ, Du X, Prasad JM, Raghu H, Palumbo JS, Smeds E, Höök M, Degen JL. Genetic elimination of the binding motif on fibrinogen for the S. aureus virulence factor ClfA improves host survival in septicemia. Blood. 2013; 121:1783-94.
  21. Geiger H, Pawar SA, Kerschen EJ, Nattamai KJ, Hernandez I, Liang HP, Fernández JÁ, Cancelas JA, Ryan MA, Kustikova O, Schambach A, Fu Q, Wang J, Fink LM, Petersen KU, Zhou D, Griffin JH, Baum C, Weiler H, Hauer-Jensen M. Pharmacological targeting of the thrombomodulin-activated protein C pathway mitigates radiation toxicity. Nat Med. 2012; 18:1123-9.
  22. George A, Pushkaran S, Konstantinidis DG, Koochaki S, Malik P, Mohandas N, Zheng Y, Joiner CH, Kalfa TA. Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease. Blood. 2013; 121:2099-107.
  23. Goyama S, Mulloy JC. Making healthy stem cells: the new role of TPO. Cell Stem Cell. 2013; 12:8-9.
  24. Guo L, Moon C, Niehaus K, Zheng Y, Ratner N. Rac1 controls Schwann cell myelination through cAMP and NF2/merlin. J Neurosci. 2012; 32:17251-61.
  25. Gutmann DH, Parada LF, Silva AJ, Ratner N. Neurofibromatosis type 1: modeling CNS dysfunction. J Neurosci. 2012; 32:14087-93.
  26. Hennigan RF, Moon CA, Parysek LM, Monk KR, Morfini G, Berth S, Brady S, Ratner N. The NF2 tumor suppressor regulates microtubule-based vesicle trafficking via a novel Rac, MLK and p38(SAPK) pathway. Oncogene. 2013; 32:1135-43.
  27. Hirai H, Kamio N, Huang G, Matsusue A, Ogino S, Kimura N, Satake S, Ashihara E, Imanishi J, Tenen DG, Maekawa T. Cyclic AMP responsive element binding proteins are involved in 'emergency' granulopoiesis through the upregulation of CCAAT/enhancer binding protein β. PLoS One. 2013; 8:e54862.
  28. Horwitz MS, Corey SJ, Grimes HL, Tidwell T. ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology. Hematol Oncol Clin North Am. 2013; 27:19-41, vii.
  29. Hoskins EE, Morreale RJ, Werner SP, Higginbotham JM, Laimins LA, Lambert PF, Brown DR, Gillison ML, Nuovo GJ, Witte DP, Kim MO, Davies SM, Mehta PA, Butsch Kovacic M, Wikenheiser-Brokamp KA, Wells SI. The fanconi anemia pathway limits human papillomavirus replication. J Virol. 2012; 86:8131-8.
  30. Ishikawa ET, Cancelas JA. Lack of communication rusts and ages stem cells. Cell Cycle. 2012; 11:3149-50.
  31. Jessen WJ, Miller SJ, Jousma E, Wu J, Rizvi TA, Brundage ME, Eaves D, Widemann B, Kim MO, Dombi E, Sabo J, Hardiman Dudley A, Niwa-Kawakita M, Page GP, Giovannini M, Aronow BJ, Cripe TP, Ratner N. MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors. J Clin Invest. 2013; 123:340-7.
  32. Jiang X, Huang H, Li Z, He C, Li Y, Chen P, Gurbuxani S, Arnovitz S, Hong GM, Price C, Ren H, Kunjamma RB, Neilly MB, Salat J, Wunderlich M, Slany RK, Zhang Y, Larson RA, Le Beau MM, Mulloy JC, Rowley JD, Chen J. MiR-495 is a tumor-suppressor microRNA down-regulated in MLL-rearranged leukemia. Proc Natl Acad Sci U S A. 2012; 109:19397-402.
  33. Joshi K, Banasavadi-Siddegowda Y, Mo X, Kim SH, Mao P, Kig C, Nardini D, Sobol RW, Chow LM, Kornblum HI, Waclaw R, Beullens M, Nakano I. MELK-dependent FOXM1 phosphorylation is essential for proliferation of glioma stem cells. Stem Cells. 2013; 31:1051-63.
  34. Katayama K, Leslie JR, Lang RA, Zheng Y, Yoshida Y. Left-right locomotor circuitry depends on RhoA-driven organization of the neuroepithelium in the developing spinal cord. J Neurosci. 2012; 32:10396-407.
  35. Keng VW, Rahrmann EP, Watson AL, Tschida BR, Moertel CL, Jessen WJ, Rizvi TA, Collins MH, Ratner N, Largaespada DA. PTEN and NF1 inactivation in Schwann cells produces a severe phenotype in the peripheral nervous system that promotes the development and malignant progression of peripheral nerve sheath tumors. Cancer Res. 2012; 72:3405-13.
  36. Keng VW, Watson AL, Rahrmann EP, Li H, Tschida BR, Moriarity BS, Choi K, Rizvi TA, Collins MH, Wallace MR, Ratner N, Largaespada DA. Conditional Inactivation of Pten with EGFR Overexpression in Schwann Cells Models Sporadic MPNST. Sarcoma. 2012; 2012:620834.
  37. Khandanpour C, Krongold J, Schütte J, Bouwman F, Vassen L, Gaudreau MC, Chen R, Calero-Nieto FJ, Diamanti E, Hannah R, Meyer SE, Grimes HL, van der Reijden BA, Jansen JH, Patel CV, Peeters JK, Löwenberg B, Dührsen U, Göttgens B, Möröy T. The human GFI136N variant induces epigenetic changes at the Hoxa9 locus and accelerates K-RAS driven myeloproliferative disorder in mice. Blood. 2012; 120:4006-17.
  38. Khandanpour C, Phelan JD, Vassen L, Schütte J, Chen R, Horman SR, Gaudreau MC, Krongold J, Zhu J, Paul WE, Dührsen U, Göttgens B, Grimes HL, Möröy T. Growth factor independence 1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia. Cancer Cell. 2013; 23:200-14.
  39. Kumar S, Filippi M. Molecular Regulation of Granulopoiesis. In: D Gabrilovich, ed. The Neutrophils: New Outlook for Old Cells. London: Imperial College Press; 2013:1-41.
  40. Kumar S, Xu J, Perkins C, Guo F, Snapper S, Finkelman FD, Zheng Y, Filippi MD. Cdc42 regulates neutrophil migration via crosstalk between WASp, CD11b, and microtubules. Blood. 2012; 120:3563-74.
  41. Largaespada D, Ratner N. Interweaving the strands: beta-catenin, an HIV co-receptor, and Schwann cell tumors. Cancer Cell. 2013; 23:269-71.
  42. Li J, Sipple J, Maynard S, Mehta PA, Rose SR, Davies SM, Pang Q. Fanconi anemia links reactive oxygen species to insulin resistance and obesity. Antioxid Redox Signal. 2012; 17:1083-98.
  43. Liu WM, Zhang F, Moshiach S, Zhou B, Huang C, Srinivasan K, Khurana S, Zheng Y, Lahti JM, Zhang XA. Tetraspanin CD82 inhibits protrusion and retraction in cell movement by attenuating the plasma membrane-dependent actin organization. PLoS One. 2012; 7:e51797.
  44. Lopez-Juarez A, Howard J, Ullom K, Howard L, Grande A, Pardo A, Waclaw R, Sun YY, Yang D, Kuan CY, Campbell K, Nakafuku M. Gsx2 controls region-specific activation of neural stem cells and injury-induced neurogenesis in the adult subventricular zone. Genes Dev. 2013; 27:1272-87.
  45. Martín-Ibáñez R, Crespo E, Esgleas M, Urban N, Wang B, Waclaw R, Georgopoulos K, Martinez S, Campbell K, Vicario-Abejón C, Alberch J, Chan S, Kastner P, Rubenstein JL, Canals JM. Helios transcription factor expression depends on Gsx2 and Dlx1&2 function in developing striatal matrix neurons. Stem Cells Dev. 2012; 21:2239-51.
  46. Mehta PA, Svahn J, Davies SM, Pang Q, Harris R, Ghezzi P, Lanza T, Ferretti E, Barabino P, Mueller R, Dufour C. Etanercept treatment in Fanconi anaemia; combined US and Italian experience. Br J Haematol. 2012; 158:809-11.
  47. Pakala SB, Rayala SK, Wang RA, Ohshiro K, Mudvari P, Reddy SD, Zheng Y, Pires R, Casimiro S, Pillai MR, Costa L, Kumar R. MTA1 Promotes STAT3 Transcription and Pulmonary Metastasis in Breast Cancer. Cancer Res. 2013; 73:3761-3770.
  48. Patel AV, Eaves D, Jessen WJ, Rizvi TA, Ecsedy JA, Qian MG, Aronow BJ, Perentesis JP, Serra E, Cripe TP, Miller SJ, Ratner N. Ras-driven transcriptome analysis identifies aurora kinase A as a potential malignant peripheral nerve sheath tumor therapeutic target. Clin Cancer Res. 2012; 18:5020-30.
  49. Patmore DM, Welch S, Fulkerson PC, Wu J, Choi K, Eaves D, Kordich JJ, Collins MH, Cripe TP, Ratner N. In vivo regulation of TGF-beta by R-Ras2 revealed through loss of the RasGAP protein NF1. Cancer Res. 2012; 72:5317-27.
  50. Plotkin SR, Blakeley JO, Evans DG, Hanemann CO, Hulsebos TJ, Hunter-Schaedle K, Kalpana GV, Korf B, Messiaen L, Papi L, Ratner N, Sherman LS, Smith MJ, Stemmer-Rachamimov AO, Vitte J, Giovannini M. Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria. Am J Med Genet A. 2013; 161:405-16.
  51. Prada CE, Jousma E, Rizvi TA, Wu J, Dunn RS, Mayes DA, Cancelas JA, Dombi E, Kim MO, West BL, Bollag G, Ratner N. Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition. Acta Neuropathol. 2013; 125:159-68.
  52. Privette Vinnedge LM, Kappes F, Nassar N, Wells SI. Stacking the DEK: from chromatin topology to cancer stem cells. Cell Cycle. 2013; 12:51-66.
  53. Romick-Rosendale LE, Lui VW, Grandis JR, Wells SI. The Fanconi anemia pathway: Repairing the link between DNA damage and squamous cell carcinoma. Mutat Res. 2013; 743-744:78-88.
  54. Schönheit J, Kuhl C, Gebhardt ML, Klett FF, Riemke P, Scheller M, Huang G, Naumann R, Leutz A, Stocking C, Priller J, Andrade-Navarro MA, Rosenbauer F. PU.1 Level-Directed Chromatin Structure Remodeling at the Irf8 Gene Drives Dendritic Cell Commitment. Cell Rep. 2013; 3:1617-28.
  55. Shang X, Marchioni F, Evelyn CR, Sipes N, Zhou X, Seibel W, Wortman M, Zheng Y. Small-molecule inhibitors targeting G-protein-coupled Rho guanine nucleotide exchange factors. Proc Natl Acad Sci U S A. 2013; 110:3155-60.
  56. Shang X, Zheng Y. Rational design of Rho GTPase-targeting inhibitors. In: Y Zheng, ed. Rational Drug Design - Methods and Protocols (Methods in Molecular Biology). New York: Springer; 2012:29-38.
  57. Shen C, Oswald D, Phelps D, Cam H, Pelloski CE, Pang Q, Houghton PJ. Regulation of FANCD2 by the mTOR Pathway Contributes to the Resistance of Cancer Cells to DNA Double-Strand Breaks. Cancer Res. 2013; 73:3393-401.
  58. Sin HS, Barski A, Zhang F, Kartashov AV, Nussenzweig A, Chen J, Andreassen PR, Namekawa SH. RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in post-meiotic spermatids. Genes Dev. 2012; 26:2737-48.
  59. Staber PB, Zhang P, Ye M, Welner RS, Nombela-Arrieta C, Bach C, Kerenyi M, Bartholdy BA, Zhang H, Alberich-Jordà M, Lee S, Yang H, Ng F, Zhang J, Leddin M, Silberstein LE, Hoefler G, Orkin SH, Göttgens B, Rosenbauer F, Huang G, Tenen DG. Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells. Mol Cell. 2013; 49:934-46.
  60. Taniguchi Ishikawa E, Chang KH, Nayak R, Olsson HA, Ficker AM, Dunn SK, Madhu MN, Sengupta A, Whitsett JA, Grimes HL, Cancelas JA. Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated beta1/beta2-integrin trafficking. Nat Commun. 2013; 4:1660.
  61. Trobridge GD, Beard BC, Wu RA, Ironside C, Malik P, Kiem HP. Stem cell selection in vivo using foamy vectors cures canine pyruvate kinase deficiency. PLoS One. 2012; 7:e45173.
  62. Unnisa Z, Clark JP, Roychoudhury J, Thomas E, Tessarollo L, Copeland NG, Jenkins NA, Grimes HL, Kumar AR. Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress. Blood. 2012; 120:4973-81.
  63. van der Loo JC, Swaney WP, Grassman E, Terwilliger A, Higashimoto T, Schambach A, Hacein-Bey-Abina S, Nordling DL, Cavazzana-Calvo M, Thrasher AJ, Williams DA, Reeves L, Malik P. Critical variables affecting clinical-grade production of the self-inactivating gamma-retroviral vector for the treatment of X-linked severe combined immunodeficiency. Gene Ther. 2012; 19:872-6.
  64. Velu CS, Grimes HL. Utilizing antagomiR (antisense microRNA) to knock down microRNA in murine bone marrow cells. In: Y Zheng, ed. Methods Mol Biol. New York: Springer; 2012:185-95.
  65. Wan H, Liu C, Wert SE, Xu W, Liao Y, Zheng Y, Whitsett JA. CDC42 is required for structural patterning of the lung during development. Dev Biol. 2013; 374:46-57.
  66. Wang B, Long JE, Flandin P, Pla R, Waclaw RR, Campbell K, Rubenstein JL. Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants. J Comp Neurol. 2013; 521:1561-84.
  67. Wang D, El-Amouri SS, Dai M, Kuan CY, Hui DY, Brady RO, Pan D. Engineering a lysosomal enzyme with a derivative of receptor-binding domain of apoE enables delivery across the blood-brain barrier. Proc Natl Acad Sci U S A. 2013; 110:2999-3004.
  68. Watson AL, Rahrmann EP, Moriarity BS, Choi K, Conboy CB, Greeley AD, Halfond AL, Anderson LK, Wahl BR, Keng VW, Rizzardi AE, Forster CL, Collins MH, Sarver AL, Wallace MR, Schmechel SC, Ratner N, Largaespada DA. Canonical Wnt/beta-catenin Signaling Drives Human Schwann Cell Transformation, Progression, and Tumor Maintenance. Cancer Discov. 2013; 3:674-689.
  69. Wunderlich M, Mizukawa B, Chou FS, Sexton C, Shrestha M, Saunthararajah Y, Mulloy JC. AML cells are differentially sensitive to chemotherapy treatment in a human xenograft model. Blood. 2013; 121:e90-7.
  70. Yolamanova M, Meier C, Shaytan AK, Vas V, Bertoncini CW, Arnold F, Zirafi O, Usmani SM, Muller JA, Sauter D, Goffinet C, Palesch D, Walther P, Roan NR, Geiger H, Lunov O, Simmet T, Bohne J, Schrezenmeier H, Schwarz K, Ständker L, Forssmann WG, Salvatella X, Khalatur PG, Khokhlov AR, Knowles TP, Weil T, Kirchhoff F, Münch J. Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses. Nat Nanotechnol. 2013; 8:130-6.
  71. Zhang F, Bick G, Park JY, Andreassen PR. MDC1 and RNF8 function in a pathway that directs BRCA1-dependent localization of PALB2 required for homologous recombination. J Cell Sci. 2012; 125:6049-57.
  72. Zhang Y, Chen A, Yan XM, Huang G. Disordered epigenetic regulation in MLL-related leukemia. Int J Hematol. 2012; 96:428-37.
  73. Zhang Y, Yan X, Sashida G, Zhao X, Rao Y, Goyama S, Whitman SP, Zorko N, Bernot K, Conway RM, Witte D, Wang QF, Tenen DG, Xiao Z, Marcucci G, Mulloy JC, Grimes HL, Caligiuri MA, Huang G. Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells. Blood. 2012; 120:1118-29.
  74. Zhao X, Zhao Z, Guo J, Huang P, Zhu X, Zhou X, Yang Z, Zhao L, Xu L, Xu J, Fu L, Zhang J, Zhang X, Dong Y, Huang G, Wang Q, Li B, Song X, Yang X, Liu S, Yi S, Yu T, Yu C, Hou L, Li J, Chen W. Creation of a six-fingered artificial transcription factor that represses the hepatitis B virus HBx gene integrated into a human hepatocellular carcinoma cell line. J Biomol Screen. 2013; 18:378-87.
  75. Zorko NA, Bernot KM, Whitman SP, Siebenaler RF, Ahmed EH, Marcucci GG, Yanes DA, McConnell KK, Mao C, Kalu C, Zhang X, Jarjoura D, Dorrance AM, Heerema NA, Lee BH, Huang G, Marcucci G, Caligiuri MA. Mll partial tandem duplication and Flt3 internal tandem duplication in a double knock-in mouse recapitulates features of counterpart human acute myeloid leukemias. Blood. 2012; 120:1130-6.

Faculty, Staff, and Trainees

Faculty Members

Yi Zheng, PhD, Professor
Leadership Co-Director, CBDI; Director, EHCB; Endowed Chair; Program Leader, Cell Signaling and Drug Discovery Program
Research Interests The physiopathological role and novel approach of therapeutic targeting of Rho GTPase and mTOR signaling networks
Paul Andreassen, PhD, Associate Professor
Research Interests Understanding mechanisms of genome instability, including Fanconi Anemia and breast cancer susceptibility. This work includes investigation of cell cycle checkpoints, especially in their role in signaling the DNA damage response. We are also investigating ubiquitin-dependent signaling in coordinating DNA damage responses and DNA repair by homologous recombination. These studies are important for understanding the genetic basis for cancer. Also, given that DNA damaging agents are extensively utilized in treating cancer, understanding the function of pathways which respond to this damage is critical for improving therapeutic strategies.
Jose Cancelas, MD, PhD, Associate Professor
Leadership Program Leader, Stem Cell Program; Director, Flow Cytometry Core Facility
Research Interests Stem Cell Program
Jay Degen, PhD, Professor
Leadership Program Leader, Hemostasis and Thrombosis Program
Research Interests The long-term objective of this research program has been to understand the mechanisms by which key hemostatic factors (e.g., prothrombin, fibrinogen, and plasminogen) contribute to diverse physiological processes (e.g., maintenance of vascular integrity, tissue repair, innate immunity) and debilitating or life-threatening pathological processes (e.g., vessel wall disease, malignancy, inflammatory disease). Because a rigorous understanding of these complex processes can only be achieved in an easily-manipulated in vivo experimental setting, a major focus of this research program has been studies of gene-targeted mouse lines lacking or expressing mutant forms of selected hemostatic factors. We and others have firmly established that multiple proteolytic targets of thrombin are coupled to the control of inflammation processes in vitro and in vivo, including fibrinogen, factor XIII, protease-activated receptors and protein C. thrombin targets to antimicrobial host defense, neuroinflammatory disease and sickle cell disease. A more comprehensive understanding of the cross-talk between the hemostatic and inflammatory systems may reveal novel, safe and effective therapeutic strategies for the treatment of a wide spectrum of diseases.
Marie-Dominique Filippi, PhD, Assistant Professor
Research Interests Stem Cell Program
Matthew Flick, PhD, Assistant Professor
Research Interests Defining the mechanisms linking coagulation and fibrinolytic system components to physiological and pathological inflammation
Hartmut Geiger, PhD, Adjunct
Leadership Director, Comprehensive Mouse and Cancer Core
Research Interests Research in the Geiger Laboratory is mostly centered around hematopoiesis and HSCs. We primarily focus our analysis on stem cell aging, leukemia and DNA damage responses in this system. We also investigate mechanisms of aging of intestinal stem cells and mechanisms of therapy-induced myelodysplastic syndrome.
Elke Grassman, PhD, HCLD, Assistant Professor
Leadership Director, Translational Trials Development and Support Laboratory
Research Interests Support Phase I/II gene transfer trials with specialized patient testing and preclinical safety studies
Fukun Guo, PhD, Assistant Professor
Research Interests Rho GTPases in T cell biology
Kakajan Komurov, PhD, Assistant Professor
Research Interests Cancer systems biology; regulatory networks, bioinformatics
Carolyn Lutzko, PhD, Associate Professor
Leadership Director, Cell Processing Core; Co-Director, Cell Manipulations Lab; Director, Development Lab
Research Interests Research is focused on using stem cells to better understand and treat inherited blood disorders. One area of research is to develop induced pluripotent stem cells from patients with blood diseases. The lab then uses these pluripotent stem cells as a renewable source for blood cells to study in the laboratory, to study disease at the cellular level, and to test potential gene and drug therapeutics. In other studies, the lab is working with other physicians and scientists to translate cell and gene therapies for blood and other diseases from the basic lab into the clinic.
Punam Malik, MD, Professor
Leadership Professor of Pediatrics, University of Cincinnati College of Medicine; Program Leader, Molecular and Gene Therapy Program; Deputy Director, Comprehensive Sickle Cell Program
Research Interests Hemoglobinopathies, Stem Cell Biology, Gene Therapy
Ruhikanta Meetei, PhD, Assistant Professor
Research Interests Signaling and Drug Discovery Program
Shyra Miller, PhD, Assistant Professor
Research Interests Cancer Biology and Neural Tumors Program
James Mulloy, PhD, Associate Professor
Leadership Co-Leader, Hematologic Malignancies Program; Associate Director, Hem/Onc/BMT Fellowship Program
Research Interests Dissection of the molecular pathogenesis of MLL-fusion AML and AML1-ETO-associated AML, using human xenograft models and experimentally generated human AML.
Nicolas Nassar, PhD, Associate Professor
Research Interests We combine biophysical, biochemical and cellular approaches to elucidate the structure/function relationship of signaling proteins and to inhibit them in disease.
Dao Pan, PhD, Assistant Professor
Research Interests Research focus is on combining translational and basic research on virus-mediated, in vivo and ex-vivo, gene transfer into stem cells, as well as their potential application for gene therapy of patients with inherited or acquired diseases, with the particular goal of ameliorating the central nervous system abnormalities and bone diseases.
Qishen Pang, PhD, Associate Professor
Research Interests Research focuses on the function of Fanconi Anemia (FA) proteins in hematopoiesis, with specific emphasis on elucidating the mechanisms by which the FA proteins regulate the hematopoietic stem cells in the context of bone marrow failure and leukemia development. These studies utilize cellular, genetic, and molecular techniques to identify and characterize critical pathways that regulate hematopoietic stem cell function.
Nancy Ratner, PhD, Professor
Leadership Program Leader, Cancer Biology and Neural Tumors; Endowed Chair
Research Interests Neurofibromatosis/Cancer Biology/Nervous system development
Damien Reynaud, PhD, Assistant Professor
Research Interests The overall goal of our research is to characterize the systemic and environmental signals that specifically affect the developing hematopoiesis at the time of birth and to investigate the contribution of these signals to the leukemogenic process in children.
Daniel Starczynowski, PhD, Assistant Professor
Research Interests Molecular and cellular basis of hematologic malignancies
Johannes van der Loo, BA, MS, PhD, Associate Professor
Leadership Director, Vector Production Facility; Director, Aseptic Processing Laboratories; Director, Viral Vector Core; Chair, Institutional Biosafety Committee
Research Interests Production of research grade viral vectors and development and scale-up of viral vector manufacturing for early phase clinical application in compliance with current Good Manufacturing Practices (cGMP)
Ronald Waclaw, PhD, Assistant Professor
Research Interests Impact of RASopathy mutations on brain development,genetic control of regional development in the mouse telencephalon, role of developmental genes during gliomagenesis
Jianqiang Wu, MD, MS, Instructor
Research Interests Preclinical trial of neurofibroma, cancer stem/progenitor cells

Joint Appointment Faculty Members

Mohammed Azam, PhD, Assistant Professor (Cancer Pathology)
Research Interests Hematology Malignancy Program
Lionel Chow, MD, PhD, Assistant Professor (Oncology)
Research Interests The Chow Lab studies High-Grade Gliomas which are aggressive brain tumors in adults and children with limited treatment options. Using a combination of novel and robust laboratory models coupled with the study of human tumor material, the lab's goals are to better understand the cellular origins and molecular underpinnings of these diseases in order to design and test novel therapies that will improve patient outcome.
Biplab DasGupta, PhD, Assistant Professor (Oncology)
Research Interests Our laboratory is interested in understanding the function of energy and nutrient sensing enzymes during normal brain development and in brain cancer. We use a variety of methods including in vitro culture systems, knockout and transgenic mouse models and ex vivo techniques to examine metabolic regulation in neural tissue.
Rachid Drissi, PhD, Assistant Professor (Oncology)
Research Interests Cancer Biology and Neural Tumors Program
Leighton Grimes, PhD, Associate Professor (Immunobiology)
Research Interests Hematology Malignancy Program
Gang Huang, PhD, Assistant Professor (Cancer Pathology)
Research Interests Cancer develops through a series of DNA and non-DNA related changes that progressively drive normal cells into highly malignant derivatives and the distinct mutations can cause the same cancer via their effects on the same regulatory network. The key regulators for blood cell development are DNA binding proteins and chromatin (proteins packed DNA) modification enzymes, which are often targeted by mutations or chromosomal translocations in human blood cancer. Research in Dr. Gang Huang's laboratory focuses on the DNA binding proteins and chromatin (proteins packed DNA) modification enzymes in blood cell normal development and cancer. This research will provide new insight into the interplay between DNA binding proteins and chromatin modification enzymes in normal blood development and leukemia. It will also help to develop drugs which will benefit the future clinical treatments.
Theodosia Kalfa, MD, PhD, Assistant Professor (Hematology)
Research Interests Hematology Malignancy Program
Ashish Kumar, MD, PhD, Assistant Professor (Bone Marrow Transplantation and Immune Deficiency)
Research Interests Hematology Malignancy program
Benjamin Mizukawa, MD, Instructor (Oncology)
Research Interests Hematological Malignancy Program
Eric Mullins, MD, Assistant Professor (Hematology)
Research Interests Hemostasis and Thrombosis Program
Joseph Palumbo, MD, Associate Professor (Hematology)
Research Interests Hemostasis and Thrombosis Program
Janos Sumegi, MD, PhD, Professor (Blood and Marrow Transplantation and Immune Deficiency)
Research Interests Hematology and Gene Therapy Program
Lisa Privette Vinnedge, PhD, Instructor (Oncology)
Research Interests Advanced breast cancer (BC) has poor survival rates and is the second leading cause of cancer deaths. Mortality is a result of tumor recurrence and disease progression, which are caused by a drug-resistant BC stem cell (BCSC) population. Identifying novel molecular mechanisms is crucial for developing new treatments that may target BCSCs, a potential candidate is the frequently upregulated, chromatin remodeling protein, DEK. My work indicates that DEK (1) promotes tumor initiation and oncogenic phenotypes, (2) increases Wnt/beta-catenin pathway activity, and (3) is an estrogen receptor (ER-alpha) target gene that promotes tamoxifen drug resistance. Of importance, DEK inhibition correlates with fewer BCSC numbers, decreased overt lung metastases in murine models, and Wnt pathway inhibition. Finally, the loss of DEK enhances the cytotoxicity of the chemotherapeutic drug cisplatin. Current work focuses on the molecular functions of DEK in BCSCs and pre-clinical studies of genetic inhibition of DEK as a means to enhance therapeutic response to several classes of drugs, thus hopefully resulting in improved patient survival.
Susanne Wells, PhD, Associate Professor (Oncology)
Research Interests The long term goal of my research program is to identify viral and cellular modifiers of epithelial cancers, and to explore the therapeutic targeting of such modifiers for the purpose of new cancer treatments. Versatile human and murine tumor models, and my board interest in viral tumor etiology and biology form the basis for our research. In past years, we have explored translational directions which offer unique training opportunities. An emerging theme is organismal and cellular preference for certain DNA repair mechanisms, a major determinant of genome instability, cancer susceptibility and response to treatment. For instance, Fanconi Anemia (AF) patients exhibit an aberrant choice of repair in every cell of the body contributes to the susceptibility of children with FA to leukemia and solid tumors, as well as to life-threatening toxicities of chemotherapy.

Trainees

  • Shailaja Akunuru, PhD, 2010, University of Cincinnati
  • Gregory Bick, BS, 2010, Case Western Reserve
  • Gasilina Anjelika, , 2011
  • Kyung-Hee Chang, PhD, PGY-5, University of Florida
  • Wei Du, MD, PhD, 2007, Tohoku University School of Medicine, Japan
  • Marthe-Sandrine Eiymo Mwa Mpollo, Grad Student, University of Montreal
  • Salim El-Amouri, PhD, PL-3, Medical University of South Carolina
  • Chris Evelyn, PhD, 2009, University of Michigan
  • Yuxin Feng, PhD, 2008, University of Cincinnati
  • Susuma Goyama, PhD, 2009, Graduate School of Medicine, University of Tokyo
  • Paritha Arumugam, PhD, CCHMC
  • Li Guo, PhD, 2006, Chinese Academy of Sciences, Shanghai, China
  • Ajay Perumbeti, MD, Northeastern Ohio Medical University
  • Vikram Kohli, PhD, Yr-1
  • Rachel Mantyla, , University of Cincinnati
  • Kimberly Breving, MS, CCHMC
  • Leesa Sampson, PhD, 2010, Vanderbilt University
  • Edwin Jousma, MS, CCHMC
  • Shan Lin, Grad Student, 2010, Tsinghua University, Beijing China
  • Kevin Link, PhD, 2007, University of Cincinnati
  • Huiqing Li, MS, Merk
  • Debra Mayes, PhD, 2006, University of Arkansas
  • Xiaoyi Chen, MD, 2012, West China Medical School, Sichuan University
  • Nicholas Olshavsky, 3rd year Post-doc, 2010, University of Cincinnati
  • Jung-Young Park, PhD, 2010, National Institutes of Health
  • Ami V. Patel, PhD, 2009, University of Louisville
  • Deanna Patmore, BS, PGY-IV, South Carolina
  • TingTing Zhang, PhD, 2012, University of Alabama at Birmingham
  • Junqi Yang, PhD, PL-1, University of Cincinnati
  • Garrett Rhyasen, BSc, PGY-2, University of Victoria
  • Wen Chai, BS, PGY-1, University of Minnesota
  • Haley Titus-Mitchell, MS, PGY-II, Wright State University
  • Melinda Varney, PhD, PDF-2, Marshall University, WV
  • Shiv Viswanathan, PhD, 2003, University of Cincinnati
  • Inuk Zandvakili, BS, 2009, University of Western Ontario
  • Shuangmin Zhang, PhD, PL-2, University of Texas
  • Xuan Zhou, BS, 2008, Tsinghua University
  • Benjamin Mizukawa, MD, 2008, University of Utah School of Medicine
  • Ryan Brooks, Grad Student, 2013
  • Jung-Mi Lee, PhD, 2012, University of Seoul, South Korea
  • Lisa Trump, PhD, PGY-2, University of Illinois, Urbana Champaign
  • Jing Fang, MD, PhD, PDF-2, Maine Medical Center Research Institute
  • Hongyan Zhu, PhD, PGY-1, University of Cincinnati
  • Mei Dai, PhD, PL-2, Institute of Materia Medica, Chinese Academy of Sciences, P.R. China
  • Jing-Fen Han, PhD, PL-2, University of Medicine & Dentistry of New Jersey
  • Juana Serrano-Lopez, PhD, PGY-5, University of Cordoba Argentina
  • Shanmuganathan Chandrakasan, MD, Children's Hospital of Michigan
  • Jed Kendall, BS, PGY-II, Brigham Young University
  • Nihal Bakeer, MD, CCHMC
  • Meghan Brundage, MS, PGY-VI, University of Cincinnati
  • Preeti Tandon, PhD, 2011, University of Cincinnati
  • Mathieu Sertorio, PhD, 2012, University Aix-Marseille II. INSERM, France
  • Kwangmin Choi, PhD, 2010, Indiana University
  • Xiaoli Li, PhD, 2011, Chinese Center for Disease Control and Prevention
  • Surya Amarachintha, PhD, 2011, Bowling Green State University
  • Navin Ravishankar, Grad Student, 2012
  • Ramesh Nayak, PhD, PGY-2, University of Texas at Tyler
  • Ashley Ficker, BS, 2009, University of Cincinnati
  • Cuiping Zhang, PhD, PGY-2, Peking Union Medical College, China
  • Ming Liu, PhD, 2010, Sichuan University China
  • Matt Grogg, PhD, 2006, University of Dayton
  • Swarnava Roy, PhD, 2010, NIH
  • Harini Raghu, PhD, 2009, University of Cincinnati
  • Swati Tiwari, , 2011, University of Delhi
  • Archana Shaesta, Grad Student, 2011, Missouri State University
  • Jeffrey Vassallo, PhD, 2012, BMS Lehy University
  • Marnie Hall, PhD, 2006, CCHMC
  • Laura Murley, PhD, 2012
  • Arun Pradhan, PhD, 2007, U Pennsylvania
  • Abdullah Ali, PhD, 2006, IISC
  • Thiyam Ramsingh, PhD, 2005

Division Collaboration

Biomedical Informatics » Bruce Aronow
Grant
BMT » Stella Davies
Grant
Immunobiology » Lee Grimes
Grant
Neonatology and Pulmonary Biology » Vladimir Kalinichenko
Thesis Committee
Division of Developmental Biology » Raphael Kopan
Thesis Committee
BMT » Ashish Kumar
Thesis Committee
Biomedical Informatics » Jaroslaw Meller
Grant, Publication
Hematology » Joe Palumbo
Grant, Publication
Oncology » John Perentesis
Grant
Developmental Biology » Jim Wells
Thesis Committee
Oncology » Susa Wells
Grant, publication
Neonatology and Pulmonary Biology » Jeffrey Whitsett
Publication
Pathology » Kathryn Wikenheiser-Brokamp
Thesis Committee
Reproductive Sciences » Satoshi Namekawa
The function of DNA repair proteins in meiosis
Bone Marrow Transplantation/Immune Deficiency » Stella Davies
Prenatal EGFR-STAT3 pathway promotes NF1 peripheral nerve tumorigenesis and transformation
Imaging Resource Center » RS Dunn
Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition
Diagnostic Immunology Lab; Bone Marrow Transplantation/Immune Deficiency » A Filipovich
Prenatal origin of Monosomy 7 in very young children
Cancer Pathology/Immunobiology » Lee Grimes
Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated membrane β1/β2-integrin expression.
Cancer Pathology/Immunobiology » Lee Grimes
Kruppel-Like-Factor 5 (Klf-5) controls hematopoietic stem cell/progenitor bone marrow homing and lodging through Rab5-mediated expression of active β1 integrin.
Biostatistics & Epidemiology/Bone Marrow Transplantation » Kim Mo
Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition.
Bone Marrow Transplantation/Immune Deficiency » Ashish Kumar
P190-B RHOGAP is critical for the hematopoietic stem and progenitor cell niche.
Radiology » D Lindquist
An EGFR-STAT3 pathway promotes NF1 peripheral nerve tumorigenesis and transformation.
Bone Marrow Transplantation and Immune Deficiency » P Mehta
Quercetin: Novel targeted chemoprevention for Fanconi anemia patients
Bone Marrow Transplantation and Immune Deficiency » P Mehta
Prenatal origin of Monosomy 7 in very young children.
Immunobiology » H Olsson
Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated membrane β1/β2-integrin expression.
Immunobiology » H Olsson
Kruppel-Like-Factor 5 (Klf-5) controls hematopoietic stem cell/progenitor bone marrow homing and lodging through Rab5-mediated expression of active β1 integrin.
Oncology » J Perentesis
Clinical Study
Oncology » J Perentesis
Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation and survival.
Human Genetics » C Prada
Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition.
Human Genetics » R Raman
P190-B RHOGAP is critical for the hematopoietic stem and progenitor cell niche.
Genetics; Pathology » T Smolarek
Prenatal origin of Monosomy 7 in very young children.
Oncology » Susa Wells
Role and Regulation of the Human DEK Proto-Oncogene
Neonate & Pulmonary Biology » J Whitsett
Kruppel-Like-Factor 5 (Klf-5) controls hematopoietic stem cell/progenitor bone marrow homing and lodging through Rab5-mediated expression of active β1 integrin.
Neonate & Pulmonary Biology » J Whitsett
Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated membrane β1/β2-integrin expression.
Genetics; Pathology » S Zimmerman
Prenatal origin of Monosomy 7 in very young children.
Hematology » Joe Palumbo
Cancer Research; Co-Investigators
Hematology » Eric Mullins
Neuroinflammatory Disease Research
Pathology » David Witte
Disease Pathogenesis Research
Pathology » S Kumar Shanmukhappa
Pathobiology of Sickle Cell Disease
Hematology » Eric Mullins
Co-Investigators
Rheumatology » Sherry Thornton
Co-Investigators
Immunology » Senad Divanovic
Co-Investigators
Hematology » Theodosia Kalfa
Set up clinical test for diagnosis of erythrocyte cytoskeleton disorder
BMT » Parinda Mehta
Support of Fanconi Anemia Program
BMT » Lisa Filipovich
Support of the SCID-X1 gene transfer trial
Human Genetics » Kejian Zhang
Support Development of Specialized Fanconi Anemia Testing
Critical Care Medicine » Basilia Zingarelli
Experiments
Immunobiology; » Lee Grimes
Provided Reagents and performed experiments
Neonatology and Pulmonary Biology » Bruce Trapnell and Jeff Whitsett
Development of Gene Therapy for hPAP and development of markers to identify lung stem cells
Molecular Cardiovascular Biology » Stephanie Ware
Development of iPSC models of cardiomyopathy
Immunobiology » Lee Grimes
Development of anti-viral Cytotoxic T Lymphocytes
BMT » Lisa Filipovich
xSCID Gene Therapy
Immunology Center - Immunobiology » Michael Jordan and Kimberly Risma
Gene Therapy for HLH
Pulmonary » Jeff Whitsett, Neeni Hensley, and Tim LeCras
Pulmonary pathology in Sickle Cell Disease
Heart Institute » Jeffrey Towbin, Tim Kimball, and Michael Taylor
Cardiac aspects of Sickle Cell Disease
Cellular and Molecular Immunology » Lee Grimes
Xenograft leukemia models
Cellular and Molecular Immunology » Clair Chougnet
Humanizing Mice
Cellular and Molecular Immunology » Julio Aliberti
Humanizing Mice
BMT » Ashish Kumar
Role of Meis1 in AML
Pathology » Gang Huang
Role of RUNX1 in AML
Rheumatology » John Harley
Immune response to EBV in humanized mice
Hematology » Joe Palumbo
Role of thrombin in AML
Cellular and Molecular Immunology » Fred Finkelman
Human mast cell development in humanized immunodeficient mice
Allergy and Immunology » Patty Fulkerson
Human eosinophil progenitor cell development in humanized immunodeficient mise
Allergy and Immunology » Nives Zimmerman
Human eosinophil cell development in humanized immunodeficient mice
Cellular and Molecular Immunology » Michael Jordan
Role of Interferon gamma in a xenograft anemia model
Human Genetics » Greg Grabowski
Gene therapy for Gaucher disease - leading to dual-PI R01 application
BMT » Stella Davies, Parinda Mehta, and Kasiani Myers
Oxidative stress and bone marrow failure in FA
Endocrinology » Susan Rose and
Endocrine defect in FA children
Pediatric Gastroenterology, Hepatology and Nutrition » Kris Steinbrecher
Inflammatory responses in FA hematopoiesis
Bioinformatics » Bruce Aronow
Publication
Ophthalmology » Richard Lang
New DOD grant funded
Radiology » Diana Lindquist
DOD grant; publication
Oncology » John Perentesis
NIH Grant; publication
Pathology; » Margaret Collins
NIH grant; publications
Cellular and Molecular Immunobiology » Lee Grimes
Gfi1 and TIFAB genetic interaction
Neonatology and Pulmonary Biology » Vladimir Kalinichenko
Studying the transcription factor Foxm1 in the development of forebrain neurons. Foxm1 expression is associated with high-grade compared to low-grade gliomas.
Oncology » Lionel Chow
Study the role of Foxm1 in a genetic model of high-grade astrocytoma
Oncology » Biplab DasGupta
Study the downstream mechanisms of abnormal Shp2 signaling caused from Shp2-GOF mutations observed in Noonan Syndrome.
Radiology » Diana Lindquist
Mouse MRI

Grants, Contracts, and Industry Agreements

Experimental Hematology Grants

Grant and Contract AwardsAnnual Direct

Akunuru, S

Training Programs in Cancer Therapeutics
T32 CA 11784609/14/12-08/31/14$48,435

Andreassen, P

14th Annual Midwest DNA Repair Symposium
R13 CA 16831704/01/12-03/31/13$6,000
FANCD2 Monoubiquitination in DNA Damage Responses
R01 HL 08558707/08/08-06/30/13$222,750

Cancelas-Perez, J

Rational Design of a Vav/Rac Inhibitor as a New Therapy
10/01/12-09/30/15$180,018

Choi, K

Regulation of Cellular Growth and Differentiation
T32 CA02062409/30/12-08/31/13$21,122

Degen, J

Analysis of Staphylococcus Aureus Host Interactions
R01 AI 02062409/30/10-08/31/13$49,971

Degen, J / Malik P (MPI)

Hemostatic Factors and Sickle Cell Disease
R01 HL 11260301/01/12-11/30/16$238,000

Feng, Y

Targeting Bone Marrow Niche to Eradicate Childhood Acute Myeloid Leukemia
06/01/13-05/31/14$25,000

Filippi, M

Regulation of Neutrophil Migration and Polarity
R01 HL 09067603/01/10-02/28/15$235,620

Flick, M

Mechanisms Linking the Hemostatic Protease Thrombin to Arthritic Disease
R01 AR 05699008/10/09-07/31/14$171,072
Cincinnati Rheumatic Disease Core Center (Core 2)
P30 AR 04736308/25/11-06/30/16$52,222

Geiger, H

Activated Protein C for Treatment of Radiation Combined Injury
R33 AI 08055709/13/10-08/31/13$77,488
Molecular Mechanisms and Therapies for Radiation-Induced Myelodysplastic Syndrome
04/01/12-03/31/17$181,818

Goyama, S

Suppressing a Tumor Suppressor RUNX1: A Novel Approach to Treat Pediatric Acute Leukemia
07/01/12-06/30/13$40,000

Hennigan, R

Regulation of Intracellular Trafficking in NF2
W81XWH131013606/01/13-05/31/16$129,421

Komurov, K

Targeting Metabolic Vulnerabilities of ERBB2-Driven Breast Cancer
04/01/13-03/31/14$40,000

Lin, S

Identification of Drug Development Pathway for Improving Prognosis of Pediatric Leukemia
05/01/12-04/30/13$30,000

Lutzko, C

NHLBI Progenitor Cell Biology Institute - Pilot Study
U01 HL 09999703/01/13-02/28/14$58,905

Malik, P

Ameliorating Sickle Nephropathy and Pulmonary Hypertension
R34 HL 10875208/18/11-06/30/14$150,000
Development of Safe and Efficient Gene Therapy Strategies
R01 HL 09848901/21/10-12/31/14$43,333
PLGF-H1F1a-mIRNA Axis in Sickle Pulmonary Hypertension
R01 HL 11137201/01/12-12/31/16$161,480
Cincinnati Cell Characterization Core
U01 HL 09999709/30/10-04/30/14$316,697
Cincinnati Cell Characterization Core - per assay
U01 HL 09999709/30/10-04/30/14$247,368

Mulloy, J

Genotype and Phenotype of Chemoresistant AML
R21 CA 16836903/01/13-02/28/15$130,500
Rac Signaling in MLL Leukemia
07/01/10-06/30/15$104,702

Olshavsky, N

Regulation of Cellular Growth and Differentiation
T32 CA 05926812/6/12-04/30/13$21,122

Pan, D

Genetic Therapy for CNS Manifestations in MPS I via BBB-Targeted Protein Delivery
R01 NS 06433009/30/08-08/31/13$214,375

Pang, Q

Role of FA Proteins in Hematopoiesis
R01 HL 07671204/01/10-03/31/15$235,620
Role of Tumor Necrosis Factor in Leukemogenesis
07/01/08-06/30/13$103,115
Targeted Improvement in Stem Cell Therapy for Leukemia and Bone Marrow Failure Syndromes
R01 CA 15753702/01/11-12/31/15$195,050

Patel, A

Neurofibromatosis Postdoctoral Traineeship
06/01/13-05/31/14$46,092

Ratner, N

Can Targeting Fat Cure MPNST?
06/01/13-05/31/14$30,000
Cincinnati Center for Neurofibromatosis Research
P50 NS 05753109/15/08-06/30/13$1,068,273
Ratner, NProject A$48,069
Cripe, TProject B$106,147
Rizvi, TProject C$81,328
Perentesis, JProject 1$297,056
Ratner, NProject 2$225,064
Ratner, NProject 3$276,814
Identification of Molecular and Cellular Contributors to Neurofibroma Formation and Growth
W81XWH121013307/01/12-06/30/15$221,965
In Vivo Testing of Anti-Oxidants in Nf1 CNS
07/01/12-06/30/13$45,455
Mitogenic Activities in Neurofibromatosis
R01 NS 02884009/15/11-07/31/16$231,250

Sampson, L

mTOR Signaling in Murine Intestinal Stem Cell and Progenitor Homeostasis
F32 DK 09787912/01/12-11/30/14$52,605

Starczynowski, D

Defining the Role and Therapeutic Potential of TNF Recep
06/01/13-05/31/16$68,182
Deregulation of TIFAB in Myelodysplastic Syndrome
07/01/11-06/30/14$50,000
Identification and Characterization of Genes in del(5q) Myelodysplastic Syndrome
R01 HL 11110312/15/11-11/30/16$238,000
Regulation and Function of TIFAB in Myelodysplastic Synd
W81XWH111046806/01/11-05/31/14$132,295

Tandon, P

Training Programs in Cancer Therapeutics
T32 CA 11784609/14/12-08/31/14$48,435

Varney, M

Environmental Carcinogenesis and Mutagenesis
T32 ES 00725005/01/12-04/30/14$6,894

Wu, J

STAT3 in Neurofibroma Tumorigenesis and Therapy
W81XWH111025907/01/11-06/30/14$132,862
Exploring the Plexiform Neurofibroma Interactone
05/15/13-05/14/15$292,910

Zheng, Y

Cincinnati Center for Excellence in Molecular Hematology
P30 DK 09097107/01/10-06/30/13$505,315
Zheng, YAdmin Core$91,497
Grabowski, GGenomics and Genetic Core$63,001
Cancelas, JCell Analysis and Sorting Core$65,112
Malik, PTranslational Core$163,824
Mulloy, JXenotransplant and Transgenic Core$68,765
Zheng, YSummer Students$30,370
Pharmacological Rejuvenation of Aged Hematopoietic Stem Cells
R34 AG 04298608/15/12-07/31/13$84,870
Rac GTPase-Specific Small Molecular Inhibitors
R01 CA 14134103/24/09-01/31/14$151,943
Training Program in Pediatric Hematologic and Oncologic Diseases
T32 HL 09180509/01/08-08/31/13$155,456
Digestive Health Center: Bench to Bedside Pilot Study
P30 DK 07839206/01/13-05/31/14$50,000

Zheng, Y / Mulloy, J

Targeting Cdc42 in Leukemia Stem Cells
R01 CA 15054703/10/10-01/31/15$189,199

Zheng,Y/ Geiger, H

Lineage Determination and Tissue HomeOstasis in the Aged Hematopoietic System
R01 AG 04011808/01/11-07/31/16$250,000
Current Year Direct$7,783,205
Industry Contracts

Mulloy, J

$164,254
$8,916
$37,668

Grassman, E

$63,176
Current Year Direct Receipts$274,014
Total$8,057,219