Experimental Hematology and Cancer Biology

Using transgenic and gene targeted mouse models to study the physiological and pathological roles of Rho GTPases and their regulators in hematopoiesis, neurogenesis, lung cancer development and small intestinal stem cell regulations mechanism based, rational design of small molecule inhibitors targeting Rho GTPase signaling modules and pathologic functions in cancer and blood diseases; mouse model studies of mTor signaling function in hematopoietic stem cells and small intestinal stem cells.

Visit the Zheng Lab.

BS: Tsinghua University, Beijing, China, 1986.

MS: Cornell University, Ithaca, NY, 1988.

PhD: Cornell University, Ithaca, NY, 1991.

Postdoctoral Fellow: Cornell University, Ithaca, NY, 1995.

View All PubMed Publications

Kesarwani M, Huber E, Kincaid Z, Evelyn CR, Biesiada J, Rance M, Thapa MB, Shah NP, Meller J, Zheng Y, Azam M. Targeting substrate-site in Jak2 kinase prevents emergence of genetic resistance. Sci Report. 2015. In press.

Konstantinidis DG, Giger KM, Risinger M, Pushkaran S, Zhou P, Dexheimer P, Yerneni S, Andreassen P, Klingmüller U, Palis J, Zheng Y, Kalfa TA. Cytokinesis failure in RhoA-deficient mouse erythroblasts involves actomyosin and midbody dysregulation and triggers p53 activation. Blood. 2015 Jul 30. [Epub ahead of print]

Barry DM, Xu K, Meadows SM, Zheng Y, Norden PR, Davis GE, Cleaver O. Cdc42 is required for cytoskeletal support of endothelial cell adhesion during blood vessel formation. Development. 2015 Aug 7. [Epub ahead of print]

Yang JQ, Kalim KW, Li Y, Zhang S, Hinge A, Filippi MD, Zheng Y, Guo F. RhoA orchestrates glycolysis for TH2 cell differentiation and allergic airway inflammation. J Allergy Clin Immunol. 2015 Jun 19. [Epub ahead of print]

Lin Y, Zheng Y. Approaches for targeting Rho GTPases in cancer drug discovery. Expert Opin Drug Discov. 2015 Sep;10(9):991-1010.

Zandvakili I, Davis AK, Hu G, Zheng Y. Loss of RhoA exacerbates, rather than dampens, oncogenic K-Ras induced lung adenoma formation in mice. PLoS One. 2015 Jun 1;10(6):e0127923.

Evelyn CR, Biesiada J, Duan X, Tang H, Shang X, Nelson S, Seibel WL, Meller J, Zheng Y. Combined rational design and a high throughput screening platform for identifying chemical inhibitors of a Ras-activating enzyme. J Biol Chem. 2015 May 15;290(20):12879-98.

Mikelis CM, Simaan M, Ando K, Fukuhara S, Sakurai A, Amornphimoltham P, Masedunskas A, Weigert R, Chavakis T, Adams RH, Offermanns S, Mochizuki N, Zheng Y, Gutkind JS. RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock. Nat Commun. 2015 Apr 10;6:6725.

Li J, Zhang L, Chen Z, Xie M, Huang L, Xue J, Liu Y, Liu N, Guo F, Zheng Y, Kong J, Zhang L. Cocaine activates Rac1 to control structural and behavioral plasticity in caudate putamen. Neurobiol Dis. 2015 Mar;75:159-76.

Chang KH, Nayak RC, Roy S, Perumbeti A, Wellendorf AM, Bezold KY, Pirman M, Hill SE, Starnes J, Loberg A, Zhou X, Inagami T, Zheng Y, Malik P, Cancelas JA. Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT₂R and cytoskeletal dysregulation. Nat Commun. 2015 Jan 9;6:5914.

Grants

Targeting Cdc42 for bone marrow transplant therapies. Principal investigator. National Institutes of Health. Apr 2015 - Apr 2020. NIH R01CA193350.

Cdc42, hematopoietic stem cell polarity and cell fate. Principal Investigator. National Institute of Health - NIDDK. Dec 2015 - Nov 2019.

Blood stem cell aging and biomarker studies. Co-Principal Investigator. National Institute of Health - NHLBI. Aug 2016 - July 2020.

Activated protein C peptides for radio-mitigation. Co-Principal Investigator. National Institute of Health - NIAID. Apr 2017 - Mar 2019.

Faculty

Paul R. Andreassen, PhD Member, Division of Experimental Hematology & Cancer Biology

Paul R. Andreassen, PhD, focuses on the relationship of DNA repair and cell cycle checkpoints to the genetic instability that underlies the development of cancer. In particular, he studies basic cellular mechanisms that respond to DNA damage, including breast cancer susceptibility (BRCA) and Fanconi anemia (FA) genes and proteins.
Visit the Andreassen Lab.

513-636-0499 paul.andreassen@cchmc.org

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Paul R. Andreassen, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-0499

Fax 513-636-3549

Email paul.andreassen@cchmc.org

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Visit the Andreassen Lab.

Clinical

Fanconi anemia; breast cancer susceptibility; genome instability; DNA damage responses; replication stress; relationship of DNA repair and chromatin; mitosis; cell biology

Research

Biography

Paul Andreassen completed his PhD in Experimental Pathology from the University of Washington (Seattle, WA) while working at the Fred Hutchinson Cancer Research Center (Seattle) and the Institut de Biologie Structurale (Grenoble, France). Dr. Andreassen then completed a research fellowship at the Dana-Farber Cancer Institute (Boston, MA) before moving to Cincinnati Children’s Hospital Medical Center in 2004.

BS: Willamette University, Salem, Oregon, 1984.

PhD: University of Washington, Seattle, Washington, 1995.

Mohammad Azam, PhD Member, Division of Experimental Hematology & Cancer Biology

Mohammad Azam, PhD, is interested in understanding molecular basis of human cancers, especially hematopoietic malignancies. His research group focuses on understanding the mechanisms of tyrosine kinase regulation, oncogene addiction and the development of cancer stem cells.

513-803-1413 mohammad.azam@cchmc.org

Elisa Boscolo, PhD Member, Division of Experimental Hematology & Cancer Biology

Elisa Boscolo, PhD, currently investigates vascular anomalies affecting children. She is devising a murine model of venous malformation. The goal of this research is to discover effective molecular therapies for this disfiguring vascular anomaly.
Visit the Boscolo Lab.

513-803-7267 elisa.boscolo@cchmc.org

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Elisa Boscolo, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-7267

Fax 513-636-3549

Email elisa.boscolo@cchmc.org

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Vascular anomalies; endothelial cell biology; mTOR signaling.
Visit the Boscolo Lab.

Biography

Elisa Boscolo received her PhD from the University of Padua, Italy. She completed her postdoctoral training and worked as instructor in Joyce Bischoff's laboratory where she investigated the cellular basis and the molecular signaling involved in infantile hemangioma formation. In May 2014, Dr. Boscolo moved to Cincinnati Children’s Hospital Medical Center to study vascular anomalies.

BS: Molecular Biology, University of Padua, Padova, Italy.

PhD: Tissue Engineering, University of Padua, Padova, Italy.

Postdoctoral Fellowship: Vascular Biology, Boston Children’s Hospital, Harvard Medical School, Cambridge, MA.

Grants

Venous Malformation (VM): murine model to identify therapies to target aberrant venous development. Principal Investigator. National Institutes of Health. 2013-2018.

Jose A. Cancelas Perez, MD, PhD Director, Research Division and Medical Director for Cell Therapies, Hoxworth Blood Center

Jose A. Cancelas Perez, MD, PhD, focuses on the study of blood-forming cells during the process of adult hematopoiesis. In particular, hematopoietic stem cells (HSC) attract clinical interest because of their potential use in stem cell and gene therapy, and because of their involvement in leukemia.
Visit the Cancelas Lab.

513-558-1324 jose.cancelas@uc.edu

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Jose A. Cancelas Perez, MD, PhD

Director, Research Division and Medical Director for Cell Therapies, Hoxworth Blood Center

Deputy Director, Hoxworth Blood Center

Leader, Stem Cell Program

Incumbent, Beatrice C. Lampkin Endowment for Stem Cell and Hematotherapy

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-558-1324

Fax 513-558-1522

Email jose.cancelas@uc.edu

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Clinical

Hematopoietic stem cell proliferation and differentiation

Research

Visit the Cancelas Lab.

MD: Autonomous University of Madrid, Spain, 1989.

Residency: Hematology and Hematotherapy, University of Alcala de Henares, Madrid, Spain, 1993.

PhD: Faculty of Medicine, University of Alcala de Henares, Madrid, Spain, 1996.

Grants

Progenitor Cell Biology Consortium Administrative Coordinating Center, NHLBI/ Subaward through Univ. Maryland. Co-Director. (Cincinnati Cell Char Core). Sep 2010 – Aug 2016. #U01 HL099997.

Lionel M.L. Chow, MD, PhD Member, Division of Oncology

Lionel M.L. Chow, MD, PhD, 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 hopefully improve patient outcome.

513-803-1369 lionel.chow@cchmc.org

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Lionel M.L. Chow, MD, PhD

Member, Division of Oncology

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-1369

Fax 513-636-3549

Email lionel.chow@cchmc.org

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Clinical

Pediatric neuro-oncology

Research

Mouse models for glioma; molecular profiling of tumor mutations; biomarkers of tumor progression; novel therapeutic agents for glioma

Biography

Lionel Chow, MD, PhD, received his medical and graduate degrees from McGill University in Montreal, Canada, where his research focused on the regulation of T-lymphocyte signaling by the intracellular tyrosine protein kinases Lck and Csk.

Following his clinical training in pediatrics and pediatric hematology / oncology at the Hospital for Sick Children in Toronto, Canada, he moved to St. Jude Children’s Research Hospital in Memphis, Tenn., to pursue his research interests.

Chow's research interests have been centered on glioblastoma multiforme, a particularly devastating form of cancer in adults and children. His work has resulted in the development of a number of novel and robust laboratory models for this disease. Using these models and interfacing with clinical trials in the Neuro-Oncology Program as well as those from national consortia such as the Children's Oncology Group (COG) and the Pediatric Brain Tumor Consortium (PBTC), Chow’s laboratory will continue research in this area with the goals of better understanding the origins of this form of cancer and improving patient outcomes.

PhD: McGill University, Montreal, Quebec, Canada, 1996.

MDCM: McGill University, Montreal, Quebec, Canada, 1997.

Residency: The Hospital for Sick Children, University of Toronto, Toronto, Canada, 1997-2000.

Clinical Fellowship: The Hospital for Sick Children, University of Toronto, Toronto, Canada, 2000-2003.

Postdoctoral Fellowship: St. Jude Children’s Research Hospital, Memphis, TN, 2003-2009.

Clinical Fellowship: St. Jude Children’s Research Hospital, Memphis TN, 2008-2009.

Certification: Pediatrics, 2000.

Biplab Dasgupta, PhD Member, Division of Oncology

Biplab Dasgupta, PhD, investigates the mechanisms of cancer development and progression. Using various state-of-the-art techniques and brain tumor as a model, his lab examines cancer stem cell metabolism, bioenergetics, signal transduction and the potential link between and cell-intrinsic and cell-extrinsic factors that influence cancer incidence and penetrance.
Visit the Dasgupta Lab.

513-803-1370 biplab.dasgupta@cchmc.org

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Biplab Dasgupta, PhD

Member, Division of Oncology

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-1370

Email biplab.dasgupta@cchmc.org

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Metabolism; cancer development

Visit the Dasgupta Lab.

Biography

Biplab Dasgupta, PhD, did doctoral research in molecular biology and immunology at Indian Institute of Chemical Biology, Calcutta, and postdoctoral research at Washington University School of Medicine, St. Louis. Dr. Dasgupta joined Cincinnati Children's in 2009 as a tenure track assistant professor of pediatrics within the University of Cincinnati College of Medicine. He rose through the ranks and is now a tenured associate professor of pediatrics. Broadly, he is interested in understanding the mechanisms of cancer development and progression. Using various state-of-the-art techniques and brain tumor as a model, his lab examines cancer stem cell metabolism, bioenergetics, signal transduction and the potential link between and cell-intrinsic and cell-extrinsic factors that influence cancer incidence and penetrance.

PhD: Indian Institute of Chemical Biology, Calcutta, 2003.

Postdoctoral Fellowship: Washington University School of Medicine, St. Louis.

Grants

Regulation of Forebrain Neurogenesis by the Energy Sensor AMP Kinase. Principal Investigator. National Institute of Neurological Disorders and Stroke (NINDS). July 2012 – June 2017.

Biguanide Sensitivity of Glioma Stem Cells (NIH). Principal Investigator. National Institute of Neurological Disorders and Stroke. Jan 2017–Dec 2022.

Exploring passenger vulnerability in GBM. Cincinnati Children's Hospital Medical Center Pilot Innovation Award. Aug 2015–Jul 2016.

Development of a lead compound active against AMP Kinase to Glioblastoma. CCTST Translational Grant Award. Apr 2016-Mar 2017.

Marie-Dominique Filippi, PhD Member, Division of Experimental Hematology & Cancer Biology

Marie-Dominique Filippi, PhD, is interested in dissecting the molecular mechanism of hematopoietic cell migration. Because hematopoietic cells are utilized for the therapy of multiple blood diseases and neutrophils are responsible for maintaining an immunocompetence status, understanding the molecular mechanism of normal hematopoietic cell functions is of potential therapeutic importance.
Visit the Filippi Lab.

513-636-0991 Marie-Dominique.Filippi@cchmc.org

Matthew J. Flick, PhD Member, Division of Experimental Hematology & Cancer Biology

Matthew J. Flick, PhD, is working to understand how hemostatic factors in the blood that are responsible for clotting also drive inflammation in the context of infection and diseases such as arthritis and fatty liver disease.

513-636-6628 matthew.flick@cchmc.org

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Matthew J. Flick, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-6628

Fax 513-803-5095

Email matthew.flick@cchmc.org

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Coagulation factors and inflammatory diseases

Biography

Research Interests and Focus:

1. Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all cancers, is rapidly becoming the second leading cause of cancer deaths in the U.S., and is estimated to cost the health care system $2.4 billion each year. Patients with PDAC have a five-year survival rate of 7%, and that number drops to 2% for individuals with metastatic disease. Unfortunately, there has been little progress in shifting patient outcome over the past 40 years, highlighting the need for innovative approaches to define the molecular pathways that influence PDAC development. PDAC is typically initiated by acinar cells acquiring an activating mutation in the KRAS protooncogene, which causes cells to transition to a duct-like state known as acinar-ductal metaplasia (ADM). ADM progresses to pancreatic intraepithelial neoplasia (PanIN) lesions that develop into PDAC. A key transcriptional response to ADM/PanIN development is the dramatically increased expression of the physiological activator of the coagulation system, Tissue Factor (TF). Our research builds on a known relationship between pancreatic cancer and high-level activity of the blood coagulation system, but is unique in that it will define newly discovered mechanisms of crosstalk by which specific coagulation factors in the TME promote PDAC pathogenesis.

2. The pervasive gram-positive bacteria Staphylococcus aureus is a common pathogen that is the causative agent for a wide spectrum of diseases including skin infections, pneumonia, bacteremia, toxic-shock syndrome and sepsis. Notably, this pathogen has evolved and maintained a number of proteins that directly engage the host hemostatic system, including factors that directly interact with the host coagulation factor fibrinogen. The long-term goal of this research program is to understand how bacterial derived proteins interact with host factors to promote bacterial virulence in the context of blood-born infections. This work will provide novel insight into the molecular pathways by which S. aureus invades and disseminates within host tissues and may shed light into novel strategies for eliminating this potentially devastating infectious agent.

3. Obesity is a worldwide epidemic linked to numerous disease sequelae, including non-alcoholic fatty liver disease (NAFLD). This spectrum disorder can progress from the simple accumulation of triglycerides within hepatocytes (i.e., steatosis), to inflammatory steatohepatitis, to organ failure secondary to irreversible liver fibrosis and cirrhosis. Dysregulation of the coagulation system has been documented in both patients with fatty liver disease and animal models of obesity, but any contribution to disease progression has remained largely undefined. Using a murine model of high fat diet (HFD)-induced obesity, this research program is testing the hypothesis that thrombin activity and fibrin deposition drive local inflammatory events promoting the progression of obesity and obesity-associated disease sequelae. Comparative studies of wild-type mice with genetically imposed deficiencies or functional alterations in prothrombin, fibrinogen and other associated coagulation factor components suggests that the thrombin-fibrinogen axis influences obesity pathogenesis by controlling local inflammatory processes that drive metabolic inflammation leading to fibrin(ogen)-mediated HFD-induced weight gain/obesity. This research has far-reaching implications for the treatment and prevention of all the downstream sequelae of obesity and even the development of diet-mediated weight gain itself.

BS: Xavier University, Cincinnati, OH.

PhD: Purdue University, West Lafayette, IN.

Post-doctoral Fellow: Cincinnati Children’s Hospital and Medical Center, Division of Developmental Biology, Cincinnati, OH.

Grants

Thrombin-dependent mechanisms of pancreatic ductal adenocarcinoma disease. Contact-Principal Investigator. National Institutes of Health. Jun 2017-May 2022. R01CA211098.

Thrombin-dependent mechanisms of pancreatic ductal adenocarcinoma disease. Principal Investigator. CCHMC GAP Award. Jan 2017-Dec 2017.

Novel anti-fibrotic mechanisms in chemical-induced liver injury. Co-Investigator. National Institutes of Health. Sep 2015-Aug 2020. R01ES017537.

Cincinnati Center of Excellence in Hemaglobinopathies Research. Co-Investigator and Project Leader. National Institutes of Health, U54 Excellence in Hemaglobinopathies Research Award. Aug 2013–May 2018. U01HL117709.

Hartmut Geiger, PhD Director, Comprehensive Mouse and Cancer Core

Hartmut Geiger, PhD, focuses on hematopoietic stem cells and their process of hematopoiesis. Blood cells are responsible for constant oxygen supply, broad and specialized immune protection, wound healing, and much more of which we might not be aware.
Visit the Geiger Lab.

513-636-1338 hartmut.geiger@cchmc.org

H. Leighton (Lee) Grimes, PhD Director, Cancer Pathology Program, Division of Experimental Hematology & Division of Pathology

H. Leighton (Lee) Grimes, PhD, focuses on the transcriptional control of normal and malignant hematopoiesis. The goal of his research is to understand how normal blood cells are formed, and to use this information to dissect the molecular pathogenesis of marrow failure and leukemia.
Visit the Grimes Lab.

513-636-6089 lee.grimes@cchmc.org

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H. Leighton (Lee) Grimes, PhD

Director, Cancer Pathology Program, Division of Experimental Hematology & Division of Pathology

Co-Leader, Program in Hematologic Malignancies of Cincinnati Children's Hospital Medical Center, Cancer and Blood Diseases Institute

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-6089

Fax 513-636-5355

Email lee.grimes@cchmc.org

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Acute myelogenous leukemia; T-cell acute lymphoblastic leuekemia; severe congenital neutropenia; hematopoiesis; myelopoiesis; lineage decision; transcription factor

Visit the Grimes Lab.

Biography

Dr. Grimes has a broad background in hematopoiesis, molecular biology, and molecular oncology including modeling of hematopoiesis, myelopoiesis and leukemia. His work on the Growth factor independent-1 (Gfi1) transcriptional repressor protein has spanned the initial identification of Gfi1 in a model of leukemia and the role of Gfi1 in normal myeloid biology, to the identification of GFI1 mutations in patients with severe congenital neutropenia (SCN) and non-immune chronic idiopathic neutropenia of adults (NI-CINA). His work utilizes Gfi1 as a molecular probe to understand both normal myeloid development and innate immune action, as well as marrow failure and transformation.

PhD: Immunology and Molecular Pathology, University of Florida, Gainesville, FL.

Postdoctoral Fellow: Fox Chase Cancer Center.

Olsson A, Venkatasubramanian M, Chaudhri VK, Aronow BJ, Salomonis N, Singh H, Grimes HL. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature. 2016 Aug 31.

Meyer SE, Qin T, Muench DE, Masuda K, Venkatasubramanian M, Orr E, Suarez L, Gore SD, Delwel R, Paietta E, Tallman MS, Fernandez H, Melnick A, Le Beau MM, Kogan S, Salomonis N, Figueroa ME, Grimes HL. DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia. Cancer Discovery. 2016; May;6(5):501-15.

Muench DE, Grimes HL. Transcriptional Control of Stem and Progenitor Potential. Curr Stem Cell Rep. 2015 Sep;1(3):139-150.

Nayak RC, Trump LR, Aronow BJ, Myers K, Mehta P, Kalfa T, Wellendorf AM, Valencia CA, Paddison PJ, Horwitz MS, Grimes HL#, Lutzko C#, Cancelas JA#. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells. J Clin Invest. 2015 Aug 3;125(8):3103-16. # shared corresponding author.

Cumaraswamy AA, Lewis AM, Geletu M, Todic A, Diaz DB, Cheng XR, Brown CE, Laister RC, Muench D, Kerman K, Grimes HL, Minden MD, Gunning PT. Nanomolar-Potency Small Molecule Inhibitor of STAT5 Protein. ACS Med Chem Lett. 2014 Sep 19;5(11):1202-1206.

Velu CS, Chaubey A, Phelan JD, Horman SR, Wunderlich M, Guzman ML, Jegga AG, Zeleznik-Le NJ, Chen J, Mulloy JC, Cancelas JA, Jordan CT, Aronow BJ, Marcucci G, Bhat B, Gebelein B, Grimes HL. Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity. J Clin Invest. 2014 Jan;124(1):222-36.

Phelan JD, Saba AI, Olsson A, Zeng H, Kosan C, Messer MS, Hildeman D, Aronow B, Möröy T, Grimes HL. Growth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors. PLoS Genetics. 2013;9(9):e1003713.

Khandanpour C*, Phelan JD*, Vassen L, Schutte J, Chen R, Horman SR, Gaudreau MC, Krongold J, Zhu J, Paul WE, Duhrsen U, Gottgens B, Grimes HL# Moroy T#. Growth factor independence 1 (Gfi1) antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia. Cancer Cell. 2013 Feb 11;23(2):200-14. * equal first author, # shared corresponding author.

Grants

Developing Novel STAT5 Protein Inhibitors for treatment of leukemias. Principal Investigator. National Cancer Institute. Sept 2014–Sept 2017. R21CA186945.

MicroRNA in Acute Myeloid Leukemia. Principal Investigator. National Cancer Institute. Jul 2011–Apr 2017. R01CA159845.

Mechanisms of granulocyte homeostasis. Principal Investigator. National Heart Lung and Blood Institute. Sept 2015–Sept 2019. R01HL122661.

A rapid spontaneous murine model of CN-AML. Principal Investigator. National Cancer Institute. Jul 2016-Jun 2019. R01CA196658.

Fukun Guo, PhD Member, Division of Experimental Hematology & Cancer Biology

Fukun Guo, PhD, studies Rho GTPases and T and B lymphocyte development and function.

513-803-1118 fukun.guo@cchmc.org

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Fukun Guo, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-1118

Email fukun.guo@cchmc.org

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Rho GTPases and T and B lymphocyte development and function

BS: Jilin University, Changchun, Jilin, China, 1994.

MS: Academy of Military Medical Sciences, Beijing, China, 1997.

PhD: Southern Medical University, Guangzhou, Guangdong, China, 2000.

Postdoctoral Research Associate: University of Tennessee, Memphis, TN, 2000-2002; Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2002-2004.

Research Associate: Southern Medical University, Guangzhou, Guangdong, China, 2000; Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2004.

Research Instructor: Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. 2005-2009.

Grants

Novel Signaling Function of Cdc42 GTPase in vivo. Principal Investigator. National Institutes of Health. 2014-2018. R01 GM108661.

Novel therapeutics of targeting mTOR pathway in T-cell leukemia. Principal Investigator. National Institutes of Health. 2015-2017. R21 CA198358-01.

Pilot Award. Principal Investigator. National Institutes of Health. 2016. P30DK090971.

Gang Huang, PhD Member, Division of Experimental Hematology & Cancer Biology

Gang Huang, PhD, focuses on genetic and epigenetic regulations of normal blood cell development and leukemia. His team demonstrated that AML1/CBFβ and mixed-lineage leukemia (MLL) protein form a regulatory complex, which is important for normal blood development and acts as a tumor suppressor in leukemia.

513-636-3214 gang.huang@cchmc.org

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Gang Huang, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Associate Professor, UC Department of Pathology & Laboratory Medicine

Phone 513-636-3214

Fax 513-636-3768

Email gang.huang@cchmc.org

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Specialties

Research in Dr. Huang’s laboratory focuses on genetic and epigenetic regulations of blood cell normal development and leukemia. The lab first demonstrated that AML1/CBFβ (a hetero-dimer transcription factor) and mixed-lineage leukemia (MLL) protein (an enzyme which methylates lysine 4 of histone H3 tails), form a regulatory complex, which is important for normal blood development and acts as a tumor suppressor in leukemia. Mutations in either one of these three genes account for majority of acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndromes (MDS).

The lab also found that the AML1/CBFβ/MLL complex regulates another transcription factor, PU.1, through the upstream regulatory region of the PU.1 gene and that the epigenetic changes of the histone tails occurring in the PU.1 regulatory region correlate with the PU.1 expression level. PU.1 expression level changes are critical for blood cell differentiation and dysregulation of PU.1 dosages leading to leukemia.

This research will provide new insight into the interplay between genetics and epigenetics in normal blood development and leukemia. It will also help to develop generic drugs for most of the AML, ALL and MDS, which will benefit the future clinical treatments.

BS: Peking University, College of Science, Beijing, P.R. China, 1991.

MS: Inner Mongolia University, Graduate School of Science, Huhhort, P.R. China, 1994.

PhD: Kyoto University, Graduate School of Medicine, Kyoto, Japan, 2001.

Grants

Role of the Hypoxia-Inducible Factor-1alpha in Myelodysplastic Syndromes. Principal investigator. National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). March 2015-Feb 2020.

A Novel Epigenetic Circuit In Acute Leukemia. Principal investigator. National Institutes of Health (NIH), National Cancer Institute (NCI). July 2014-June 2017.

Theodosia A. Kalfa, MD, PhD Co-Director, Erythrocyte Diagnostic Laboratory

Theodosia A. Kalfa, MD, PhD, focuses on the study of intracellular signals in erythropoiesis and mature red blood cells, specifically the signals conducted by Rho GTPases regulating terminal erythroid maturation and enucleation. Her lab also studies the role of Rac GTPases in generation of reactive oxygen species (ROS) within red blood cells from patients and animal models with sickle-cell disease along with the signaling mechanisms and consequences of increased ROS in sickle cells.
Visit the Kalfa Lab.

513-636-0989 theodosia.kalfa@cchmc.org

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Theodosia A. Kalfa, MD, PhD

Co-Director, Erythrocyte Diagnostic Laboratory

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-0989

Fax 513-636-3549

Email theodosia.kalfa@cchmc.org

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Signaling in erythrocytes; erythropoiesis; sickle cell disease; reactive oxygen species

Visit the Kalfa Lab.

MD: Aristotle University Medical School, Thessaloniki, Greece, 1990.

PhD: Aristotle University Medical School, Thessaloniki, Greece, 1997.

Residency: University Of North Carolina, Chapel Hill, NC, 1999.

Fellowship: Duke University Medical Center, Durham, NC, 2003.

Certification: Hematology / oncology, American Board of Pediatrics, 2004; Pediatrics, American Board of Pediatrics, 2000; ECFMG Certification, 1995.

Licenses: Full and unrestricted medical license (OH Medical Board), 2003-present; full and unrestricted license of medical practice in Greece, 1990-present.

Grants

Rho GTPases in Terminal Erythroid Maturation. Principal Investigator. NIH/NHLBI. Sep 2012-Jun 2016. #1R01HL116352.

Cincinnati Center of Excellence in Hemoglobinopathies Research. Co-investigator. NIH/NHLBI. Aug 2013–May 2018. # U01 HL117709.

Kakajan Komurov , PhD Member, Division of Experimental Hematology & Cancer Biology

Dr. Komurov's lab integrates computational and experimental approaches to characterize targetable cancer vulnerabilities. Their driver projects include exploiting oncogene-induced stress pathways in cancer therapy, and the study of mechanisms, implications and therapeutic vulnerabilities imposed by the severe epigenetic defects in a subset of cancers.
Visit the Komurov Lab.

513-803-5122 kakajan.komurov@cchmc.org

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Kakajan Komurov , PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-5122

Email kakajan.komurov@cchmc.org

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Computational and experimental approaches to characterize targetable cancer vulnerabilities; oncogene-induced stress pathways in cancer therapy; the study of mechanisms, implications and therapeutic vulnerabilities imposed by the severe epigenetic defects in a subset of cancers

Visit the Komurov Lab.

Biography

Dr. Komurov's lab focuses on the systems biology of cancer. We develop and employ computational data mining tools to interrogate clinically exploitable cancer mechanisms from cancer genomics data, and use experimental approaches in vitro and in animal models for their molecular characterization. Specifically, we are studying the core aberrations in the genomic, RNA and protein homeostasis networks in cancers, their role in cancer pathogenicity and therapy response, and the synthetic vulnerabilities imposed by these defects on the tumor cell. In addition, we are developing computational methods and software to enable intuitive and effective functional mining of genomic data.

PhD: The University of Texas Southwestern Medical Center, Dallas, TX.

Grants

Modeling and targeting the hexosamine pathway in drug resistance. Principal Investigator. Susan G. Komen for the Cure. Aug 2013-Jul 2016. CCR13263034.

Exploiting proteotoxic stress in therapy-refractory HER2+ breast cancers. Principal Investigator. National Cancer Institute. Apr 2015-Mar 2020. 1R01CA193549-01.

Global Transcript Shortening in cancers. Principal Investigator. Cincinnati Children's Hospital Medical Center RIP award. Sep 2015-Aug 2016.

Ashish R. Kumar, MD, PhD Director, Langerhans Cell Histiocytosis Center

Ashish R. Kumar, MD, PhD, is a pediatric hematologist/oncologist whose lab is investigating the biology childhood cancers and blood diseases. The current focus of research in the lab is on infant leukemia and LCH.
Visit the Kumar Lab.

513-803-1631 ashish.kumar@cchmc.org

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Ashish R. Kumar, MD, PhD

Director, Langerhans Cell Histiocytosis Center

Director, Hematology/Oncology Fellowship Program

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-1631

Fax 513-636-3549

Email ashish.kumar@cchmc.org

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Clinical

Childhood cancer and blood disorders; immune deficiency

Research

Leukemia biology; cancer biology

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Biography

Visit the HLH Center of Excellence.

Dr. Kumar received his medical degree from L.T.M. Medical College, Mumbai, India, his PhD in anatomy and cell biology from the University of Iowa, pediatric residency training at the Mayo Clinic and fellowship in pediatric hematology / oncology / BMT at the University of Minnesota. He was appointed to the faculty of the University of Minnesota in the Department of Pediatrics where he was a member of the programs in pediatric leukemia and global pediatrics. He is currently an associate professor of pediatrics in the Division of Bone Marrow Transplantation and Immune Deficiency at Cincinnati Children's within the University of Cincinnati College of Medicine. Dr. Kumar’s laboratory is engaged in researching the biology of infant leukemia. Discoveries made in his laboratory have significantly enhanced the current understanding of leukemia. Dr. Kumar is also active in education. He has delivered invited lectures and grand round presentations on various topics.

Learn more about the 700 Miles to Hope Bike Ride.

Dr. Kumar has been elected by peers for inclusion in the Best Doctors in America List.

MD: LTM Medical College, Mumbai, India.

Residency: Mayo Clinic, Rochester, MN.

Fellowship: University of Minnesota, Minneapolis, MN.

PhD: University of Iowa, Iowa City, IA.

Certification: General Pediatrics; Pediatric Hematology/Oncology Subspecialty.

Licenses: State of Ohio; State of Minnesota.

Grants

Role of MEIS1 in hematopoiesis and hematopoietic transformation. Principal Investigator. National Institutes of Health/National Heart, Lung, and Blood Institute. Jul 2012-Jun 2017.

Novel therapeutics of targeting mTOR pathway in T-cell leukemia. Co-investigator. National Institutes of Health/National Cancer Institute. Jul 2015-Jun 2017.

Adam Lane, PhD Member, Division of Bone Marrow Transplantation and Immune Deficiency

Adam Lane, PhD, has methodological research interests in designs for phase I/II clinical trials, survival analysis and structural equation modeling. Dr. Lane is also a dedicated collaborator with both clinical and basic science researchers in bone marrow transplantation, hematology, oncology and cancer biology.

513-803-1828 adam.lane@cchmc.org

Qing Richard Lu, PhD Beatrice C. Lampkin endowed Chair in Cancer Epigenetics

Qing Richard Lu, PhD, and his lab study the transcriptional and signaling regulatory networks that control gliogenesis (oligodendrocyte, astrocyte and Schwann cell), brain cancer stem/initiating cell growth and myelinogenesis. Dr. Lu lab utilizes transgenic and gene targeting mouse models to understand the molecular mechanisms underlying demyelinating diseases and brain tumorigenesis and to develop new therapies for neurodegenerative diseases and brain cancers.

Visit the Lu Lab.

513-636-7684 richard.lu@cchmc.org

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Qing Richard Lu, PhD

Beatrice C. Lampkin endowed Chair in Cancer Epigenetics

Scientific Director, Brain Tumor Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7684

Fax 513-636-3549

Email richard.lu@cchmc.org

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Visit the Lu Lab.

BS: Peking Normal University, Beijing, China, 1988.

MS: Rutgers University, Piscataway, NJ, 1993.

PhD: Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, 1997.

Postdoctoral Fellow: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 1997-2002.

Wang H, Moyano A, Ma Z, Deng Y, Lin Y, Zhang L, Zhao C, He X, Ma Z, Lu F, Xin X, Zhou W, Yoon S, Bongarzone E, Lu QR. miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS. Developmental Cell. 2017 Mar 27;40(6):566-582.

Deng Y*, Wu L*, Bai* S, Zhao C, Wang H, Wang J, Xu L, Zhou W, Xin M, Lu QR. A Reciprocal Regulatory Loop Between TAZ/YAP and G protein Gαs Regulates Schwann Cell Proliferation and Differentiation. Nature Communications. 2017;8:15161.

He D, Wang J, Lu Y, Deng Y, Zhao C, Xu L, Chen Y, Hu Y, Zhou W, Lu QR. lncRNA Functional Networks in Oligodendrocytes Reveal Stage-Specific Myelination Control by an lncOL1/Suz12 Complex in the CNS. Neuron. 2017 Jan 18;93(2):362-378.

Jiang M, Liu L, He X, Wang H, Lin W, Wang H, Yoon SO, Wood TL, Lu QR. Regulation of PERK-eIF2α Signaling by Tuberous Sclerosis Complex-1 Controls Homeostasis and Survival of Myelinating Oligodendrocytes. Nat Commun. July 2016;7:12185.

Wu LM, Wang J, Conidi A, Zhao C, Wang H, Ford Z, Zhang L, Zweier C, Ayee BG, Maurel P, Zwijsen A, Chan JR, Jankowski MP, Huylebroeck D, Lu QR. Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination. Nat Neurosci. 2016 Aug;19(8):1060-72.

Lu F, Chen Y, Zhao C, Wang H, He D, Xu L, Wang J, He X, Deng Y, Lu EE, Liu X, Verma R, Bu H, Drissi R, Fouladi M, Stemmer-Rachamimov AO, Burns D, Xin M, Rubin JB, Bahassi EM, Canoll P, Holland EC, Lu QR. Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma. Cancer Cell. 2016; 9;29(5):669-83.

He D, Marie C, Zhao C, Kim B, Wang J, Deng Y, Clavairoly A, Frah M, Wang H, He X, Hmidan H, Jones BV, Witte D, Zalc B, Zhou X, Choo DI, Martin DM, Parras C, Lu QR. Chd7 Cooperates with Sox10 and Regulates the Onset of CNS Myelination and Remyelination.Nature Neuroscience. 2016.

Zhao C, Deng Y, Liu L, Yu K, Zhang L, Wang H, He H, Wang J, Lu C, Wu LN, Weng Q, Mao M, Li J, van Es JH, Xin M, Parry L, Goldman SA, Clevers H, Lu QR. Dual Regulatory Switch Through Interactions of Tcf7l2/Tcf4 with Stage-Specific Partners Propels Oligodendroglial Maturation.Nature Communications. 2016;7:10883.

Zhang L*, He X*, Liu L, Jiang M, Zhao C, Wang H, He D, Zheng T, Zhou X, Hassan A, Ma Z, Xin M, Sun Z, Lazar MA, Goldman SA, Olson EN, Lu QR. Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch.Developmental Cell. 2016 Feb 8;36(3):316-30.

He X, Zhang L, Chen Y, Remke M, Shih D, Lu F, Wang H, Deng Y, Yu Y, Xia Y, Wu X, Ramaswamy V, Hu T, Wang F, Zhou W, Burns DK, Kim SH, Kool M, Pfister S, Weinstein LS, Pomeroy S, Gilbertson R, Rubin JB, Hou Y, Wechsler-Reya R, Taylor MD, Lu QR. The G-protein Alpha Subunit Gsα Is A Tumor Suppressor In Sonic Hedgehog driven Medulloblastoma.Nature Medicine. 2014 Sep;20(9):1035-42.

Grants

Molecular Mechanisms of Oligodendrocyte Differentiation and Myelination. Principal Investigator. National Institutes of Health (NINDS). Sep 2015-Aug 2020. 1R01NS072427.

Chromatin Remodeling Control of CNS Myelination and Remyelination. Principal Investigator. National Institutes of Health (NINDS). Apr 2012–Mar 2020. 1R01NS075243-01.

A Novel Model of Medulloblastoma to Define Cancer Pathways and Molecular Targets. Principal Investigator. National Institutes of Health (NINDS). Apr 2012–Mar 2018. 1R01NS078092.

Carolyn M. Lutzko, PhD Director, Cell Manipulation Laboratory and Translational Development, Translational Core Laboratory

Carolyn M. Lutzko, PhD, studies the regulation of human pluripotent stem cells, somatic cell reprogramming in iPSC, human embryonic stem cell physiology and differentiation, hESC, and cystic fibrosis.

513-803-2420 carolyn.lutzko@cchmc.org

Punam Malik, MD Director, Cincinnati Comprehensive Sickle Cell Center

Punam Malik, MD, works to correct the gene responsible for sickle cell anemia. One of the lab’s major projects uses gene therapy to treat sickle cell disease. The lab is also interested in gene therapy for other diseases. She has developed various methods for delivering corrective genes to cells, improving methods for gene therapy in general.

513-636-1333 punam.malik@cchmc.org

Ruhikanta A. Meetei, PhD Member, Division of Experimental Hematology & Cancer Biology

Ruhikanta A. Meetei, PhD, focuses on functional analysis of Fanconi anemia gene products. The major research focus includes identification of new FA genes and signal transduction pathways that regulate DNA-damage-induced activation of the FA-core complex.

513-636-1768 ruhikanta.meetei@cchmc.org

Benjamin E. Mizukawa, MD St. Baldrick’s Foundation Scholar

Benjamin E. Mizukawa, MD, is trained in pediatric hematology/oncology with a research emphasis in leukemia biology and novel therapeutics. His work is focused on understanding the role of small Rho GTPases in myeloid leukemia development and progression, with the translational goal of identifying new targets for drug development.

513-636-1335 benjamin.mizukawa@cchmc.org

James C. Mulloy, PhD Co-Leader, Hematological Malignancy Program

James C. Mulloy, PhD, focuses on using human hematopoietic stem cells to model leukemia. His lab is expressing the fusion protein, AML1-ETO, in human CD34+ stem cells by retroviral transduction and characterizing the genetic and functional alterations that occur due to expression of this oncogene.
Visit the Mulloy Lab.

513-636-1844 james.mulloy@cchmc.org

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James C. Mulloy, PhD

Co-Leader, Hematological Malignancy Program

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-1844

Fax 513-636-3768

Email james.mulloy@cchmc.org

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Visit the Mulloy Lab.

BA: St. Anselm College, Manchester, NH, 1986.

MS: Rutgers University-University of Medicine and Dentistry, New Brunswick, NJ, 1989.

PhD: Rutgers University-University of Medicine and Dentistry, New Brunswick, NJ, 1992.

Grants

Conferring in vivo metabolic resistance to a highly selective anti-AML agent. Co-Investigator. National Institutes of Health/National Cancer Institute. May 2014-Apr 2017.

Rapid Suppression of Food Allergy with Anti-Fc Epsilon Rl Alpha Antibody. Co-Investigator. Food Allergy Research & Education Inc. Apr 2014-Mar 2017.

Suppression of IgE-Mediated Disease by Polyclonal Rapid Desensitization. Co-Investigator. National Institutes of Health/National Institute of Allergy and Infectious Diseases. Jul 2014-Jun 2019.

A new Hydrogen Peroxide-activated Agent that Selectively. Co-Principal Investigator. Center for Clinical and Translational Science and Training. Jul 2015-Jun 2016.

Nicolas Nassar, PhD Member, Division of Experimental Hematology & Cancer Biology

Nicolas Nassar, PhD, is a structural biologist interested in understanding the structure/function of signaling proteins, how they specifically bind and recognize regulators and targets, and in finding ways to inhibit their signaling in disease. His lab combines X-ray crystallography, site-directed mutagenesis, enzyme kinetics, and other biophysical techniques in its studies.

513-636-6597 nicolas.nassar@cchmc.org

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Nicolas Nassar, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-6597

Fax 513-636-3549

Email nicolas.nassar@cchmc.org

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Biography

The major focus of our laboratory is to understand the regulation and signaling of the GTP-binding protein Ras and other Ras-like GTPases and to find small molecules that inhibit their activity in human cancers. Signaling by Ras-like GTPases is key to almost every cellular process and Ras is among the most mutated genes in human cancer. Despite this, a small molecule specifically targeting Ras activity has yet to enter clinical trials. Our research efforts encompass several methodologies, including protein crystallography, biophysical and biochemical studies, cellular functional assays, and ultimately, high throughput screenings of chemical libraries of small compounds that bind to and modulate GTPase signaling in cell line models.

We have identified several compounds that bind in vitro to Ras, inhibit cell proliferation of lung and other Ras-transformed cell lines, and decrease the activation of Erk-1/-2 and PI3K/AKT. Several ongoing questions stem from this finding: (i) we want to establish the mechanism of action(s) of these compounds. What gene or cellular process do they activate or silence downstream of Ras? Do they bind to Ras in cells and how specific is their binding? (ii) We are in the process of translating our findings to several disease models where Ras is hyperactivated, including both solid tumors such as lung adenocarcinomas, and MPNSTs and leukemias such as B-ALL.

We are also interested in the structure/function relationship of the multidomain protein tyrosine phosphatase (PTP) UBASH3B/Sts-1. Sts-1 was shown to be a target in triple negative breast cancer (TNBC). Our research is geared towards identifying small molecule inhibitors of the phosphatase activity of Sts-1. We have identified one such compound that inhibits the phosphatase activity of Sts-1 in vitro, decreases TNBC cell proliferation and decreases overall levels of phosphorylated proteins. We are currently testing structural analogs of our lead compound to further improve its potency.

PhD: University Joseph Fourier, Grenoble,France, 1992.

Postdoc: Max Plank Institut, Dortmund, Germany, 1996.

Research Associate: Cornell University, Ithaca, NY, 2000.

Assistant Professor: Stony Brook University, NY, 2006.

Research Assistant Professor: Stony Brook University, Stony Brook, NY, 2010.

Dao Pan, PhD Member, Division of Experimental Hematology & Cancer Biology

Dao Pan, PhD, has long term research interests in combining translational and basic research on virus-mediated gene transfer and disease treatment for mucopolysaccharidoses disorders, which are often associated with systemic and central nerve system abnormalities, and early childhood death.
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513-636-6315 dao.pan@cchmc.org

Qishen Pang, PhD Member, Division of Experimental Hematology & Cancer Biology

The Pang Laboratory is focused on elucidating the mechanisms by which the Fanconi proteins regulate hematopoietic stem cells in the context of bone marrow failure and leukemia development. The goal of the research is to identify novel pharmaceutical targets for the treatment of patients with Fanconi anemia and other bone marrow failure syndromes. Several current projects will utilize cellular, genetic, and molecular techniques to identify and characterize critical pathways that regulate hematopoietic stem cells function, using knockout mice and xenotransplant models.
Visit the Pang Lab.

513-636-1152 qishen.pang@cchmc.org

Nancy Ratner, PhD Co-Director, Rasopathy Program

Nancy Ratner, PhD, is working to define the interactions between glial cells and axons during nervous system development and how those interactions go awry in disease. Her goal is to develop novel therapies for patients with nervous system diseases.

Visit the Ratner Lab.

513-636-9469 nancy.ratner@cchmc.org

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Nancy Ratner, PhD

Co-Director, Rasopathy Program

Program Leader, Cancer Biology and Neural Tumors Program

Beatrice C. Lampkin Chair, Cancer Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-9469

Fax 513-636-3549

Email nancy.ratner@cchmc.org

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Clinical/Translational

Preclinical testing in neurofibromatosis tumors

Research

Genetic mutations in tumor suppressor genes; development of the nervous system; peripheral nerve tumor formation

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Biography

Nancy Ratner, PhD, is interested in understanding mechanisms of peripheral nerve tumor (neurofibroma) formation in neurofibromatosis type 1 (NF1), a common inherited disorder in which children are predisposed to cancer of the nervous system, to learning problems, bone disorders, and other cancers. She identified EGFR and MEK as potential therapeutic targets in NF1 peripheral nerve tumorigenesis, and has developed cell culture and mouse models of NF1 nerve tumorigenesis. Her laboratory has also used analysis of gene expression to identify critical genes in neurofibroma and their malignant derivatives, MPNST.

Dr. Ratner received her bachelor's from Brown University, her doctorate from Indiana University, and was a postdoctoral fellow at Washington University in St. Louis. She was a member of the faculty at the University of Cincinnati from 1987 to 2004. Dr. Ratner is currently a professor in the Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, and the program leader for Cancer Biology and Neural Tumors Program in the Cancer and Blood Diseases Institute where she holds the Beatrice C. Lampkin Endowed chair in cancer biology and serves as PI of the NINDS P50 “Cincinnati Center in NF Research.”

Dr. Ratner is an active member of the International Consortium on the Molecular Biology of NF1, NF2, and Schwannomatosis and was a member of the advisory board for the National Neurofibromatosis Foundation (now Children’s Tumor Foundation) from 1989 to 2007. She chaired the Department of Defense Neurofibromatosis Research Program Integration Panel in 2008, and currently serves as a member of the James McDonnell Brain Tumor Research Advisory Board. She received the von Recklinghausen Award from the Children’s Tumor Foundation in 2010 and the Jacob K. Javits Neuroscience Investigator Award (NIH-NINDS MERIT Award) in 2014.

PhD: Indiana University, 1982.

BA: Brown University, 1975.

Fellowship: Washington University St. Louis, 1982-1987.

Grants

Mitogenic Activities in Neurofibromatosis. Principal Investigator. Sept 2011-2016. NIH-R01 NS 28840-20.

Preclinical Testing: GEM-Neurofibroma. Principal Investigator. Children's Tumor Foundation. Aug 2013-Jul 2016.

Identification of Neurofibroma Growth and Drug Resistance Pathways. Principal Investigator. Neurofibromatosis Therapeutic Acceleration Program (NTAP). Apr 2014-Mar 2016.

Ras Proteins in Nerve Tumorigenesis. Principal Investigator. Apr 2014-Mar 2019. 1R01 NS083580-01A1.

Novel Combinatorial Therapies for Malignant Peripheral Nerve Sheath Tumors. Co-Principal Investigator. Jul 2014-Jun 2016. 1R21NS084885-01A1.

Disordered Wnt/b-catenin signaling in MPNST Development and Maintenance. Co-Principal Investigator. Oct 2014-Sep 2019. 1R01NS086219-01A1.

Can targeted therapy prevent neurofibroma growth in mice? Principal Investigator. Neurofibromatosis Therapeutic Acceleration Program (NTAP). Sep 2014-Aug 2016.

Damien Reynaud, PhD Member, Division of Experimental Hematology & Cancer Biology

Damien Reynaud, PhD, is an experimental hematologist interested in dissecting the cell-intrinsic and micro-environmental cues that regulate normal and pathological blood production. His research is focused on the molecular mechanisms that control normal B cell lymphopoiesis and how corruption of these mechanisms contributes to the development of acute lymphoblastic leukemia in children and adults.

513-803-4498 damien.reynaud@cchmc.org

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Damien Reynaud, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-4498

Fax 513- 636-3768

Email damien.reynaud@cchmc.org

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Specialties

Hematopoietic stem and progenitor cells; mechanisms of leukemic progression B cell development

Biography

Dr. Reynaud’s long-standing research interest is to understand the mechanisms controlling cell fate decisions in the hematopoietic system. During his graduate and post-graduate training, he worked to decipher the transcriptional regulatory networks that (i) control self-renewal activity and lineage specification in hematopoietic stem cells and (ii) regulate progenitor differentiation during the establishment of the natural and adaptive immune system. More recently he investigated the deregulation in stem and progenitor cell activity that, in adults, leads to the development of abnormal hematopoiesis and eventually to chronic myeloid leukemia. This work uncovered an unexpected contribution of the pro-inflammatory environment to leukemia development. Notably he identified a novel function for the pro-inflammatory cytokine IL-6 in reprogramming the fate of an early leukemic progenitor by promoting myeloid development at the expense of lymphoid differentiation. Following this work, the overall goal of his research at Cincinnati Children’s Hospital Medical Center is to characterize how micro-environmental signals regulate normal B lymphoid and how corruption of these signals contribute to the initiation, maintenance and progression of acute lymphoblastic leukemia.

PhD: University Renee Descartes, Paris, France, 2004.

Postdoctoral Fellow: University of Chicago/HHMI, Chicago, IL, 2008; University of California, San Francisco, San Francisco, CA, 2013.

View Dr. Reynaud's PubMed Publications

Daniel T. Starczynowski, PhD Member, Experimental Hematology and Cancer Biology

Daniel T. Starczynowski, PhD, is a cancer biologist who has a basic research programs with a translational emphasis in myeloid hematological malignancies. His lab’s major effort is studying the molecular and cellular basis of myelodysplastic syndromes, bone marrow failure syndromes and acute leukemia. The goal is to identify candidate genes and understand their contribution to myeloid malignancies.
Visit the Starczynowski Lab.

513-803-5317 daniel.starczynowski@cchmc.org

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Daniel T. Starczynowski, PhD

Member, Experimental Hematology and Cancer Biology

Co-Leader, Program in Hematologic Malignancies of Cincinnati Children's Hospital Medical Center, Cancer and Blood Diseases Institute

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-5317

Email daniel.starczynowski@cchmc.org

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Visit the Starczynowski Lab.

Biography

Daniel T. Starczynowski, PhD, received his PhD in molecular biology from Boston University. He studied the NF-kB family of transcription factors and their role in B-cell lymphomas. During his postdoctoral fellowship at the BC Cancer Research Center, Dr. Starczynowski identified and characterized novel candidate genes in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

Following his postdoctoral training, Dr. Starczynowski joined the faculty at Cincinnati Children’s Hospital Medical Center and at the University of Cincinnati as an Assistant Professor. Dr. Starczynowski’s laboratory investigates the molecular and cellular basis of hematologic malignancies with the goal to advance novel therapeutic strategies.

BS: Fairleigh Dickinson University, Teaneck, NJ, 2000.

PhD: Boston University, Boston, MA, 2006.

Postdoctoral Fellow: University of British Columbia/BC Cancer Research Centre, Vancouver, Canada, 2010.

Ronald R. Waclaw, MS, PhD Member, Division of Experimental Hematology & Cancer Biology

Ronald R. Waclaw, MS, PhD, is a developmental neurobiologist who has a research program in forebrain development and function. His lab studies the molecular genetic mechanisms in forebrain progenitor cell differentiation. One focus of his lab is to determine the effect of known “RASopathy” genes, which result in abnormalities in RAS/MAPK signaling, on brain development and brain tumor formation.

513-803-3336 ronald.waclaw@cchmc.org

Susanne Wells, PhD Director, Epithelial Carcinogenesis and Stem Cell Program

Susanne Wells, PhD, focuses on new targets of the HPV E6/E7 oncogenes, and characterizing these as potential risk factors for HPV infection and transformation. Research approaches include bioinformatics; analyses of primary, transformed and 3D cell culture systems; and mouse tumor models to facilitate translational endeavors.
Visit the Wells Lab.

513-636-5986 susanne.wells@cchmc.org

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Susanne Wells, PhD

Director, Epithelial Carcinogenesis and Stem Cell Program

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-5986

Fax 513-636-3549

Email susanne.wells@cchmc.org

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Specialties

Squamous cell carcinoma; mechanisms by which the HPV oncogenes subvert the host cell machinery to promote abnormal cell growth and cancer; role of specific cellular HPV targets in viral replication and cellular transformation

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Biography

Susanne Wells graduated from the University of Konstanz, Germany, with a degree in biology. She completed her PhD in molecular biology at the State University of Stony Brook, NY, and her postdoctoral fellowship at Harvard Medical School, MA. Dr. Wells moved to Cincinnati Children's Hospital Medical Center in 2002 to study human papillomavirus infection and associated carcinogenesis.

BS: Biology, University of Konstanz, Germany, 1992.

PhD: Molecular Genetics, State University of Stony Brook, NY, 1997.

Postdoctoral Fellowship: Molecular Virology, Harvard Medical School, Boston, MA.

Grants

Role and regulation of the human DEK proto-oncogene. Principal Investigator. National Institutes of Health. 2012-2017. 2R01 CA116316.

Jianqiang Wu, MD, MS Member, Division of Experimental Hematology & Cancer Biology

Jianqiang Wu, MD, MS, focuses on preclinical therapeutic trials studying neurofibroma and cancer stem cell(s) in neurofibroma.

513-636-0955 jianqiang.wu@cchmc.org

Mei Xin, PhD Member, Division of Experimental Hematology & Cancer Biology

Mei Xin, PhD, studies the mechanisms of heart growth, regeneration and vascular development. Dr. Xin’s research focuses on the identification and characterization of critical transcriptional and post-transcriptional molecules, as well as the signaling networks that control cardiovascular development and disease. These studies may provide insight towards therapeutic interventions for cardiovascular disorders.

513-803-3464 mei.xin@cchmc.org

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Mei Xin, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-3464

Fax 513-636-3549

Email mei.xin@cchmc.org

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Regulation of organogenesis such as cardiovascular and heart growth and regeneration, and the nervous system development

Biography

Mei Xin received her PhD from the University of Texas Southwestern Medical Center at Dallas. She completed her postdoctoral training in Eric Olson’s laboratory where she investigated microRNAs and Hippo signaling molecules regulating cardiovascular development and regeneration. In August 2013, Dr. Xin moved to Cincinnati Children’s Hospital Medical Center to study organogenesis including cardiovascular and peripheral nervous system development and diseases.

MS: Robert Wood Johnson Medical School, Piscataway, NJ.

PhD: The University of Texas Southwestern Medical Center, Dallas, TX.

Postdoctoral Fellowship: The University of Texas Southwestern Medical Center, Dallas, TX.

Grants