Molecular and Gene Therapy Program
Program Leader: Punam Malik, MD
Molecular and Gene Therapy Faculty
- Punam Malik, MD, Associate Professor, Program Leader
- Christopher Baum, MD, Adjunct Associate Professor
- Timothy Cripe, MD, Associate Professor*
- Timothy M. Crombleholme, MD, FACS, FAAP , Professor*
- Thomas Moritz, MD, Adjunct Assoicate Professor
- Dao Pan, PhD, Assistant Professor
- Christof von Kalle, MD, Adjunct Assoicate Professor
- David A. Williams, MD, Professor, Director, Experimental Hematology
The Molecular and Gene Therapy Program began in 2002, with the recruitment of Dr. David Williams as the Director of the Division of Experimental Hematology (EH). Subsequently Dr. Christof von Kalle was recruited as the Program Leader, and Drs. Christopher Baum, Patrick Kelly, Dao Pan were recruited to the program. Drs. Timothy Crombleholme, Thomas Moritz and Timothy Cripe joined the program as adjunct/joint appointees. Dr. Kalle moved to an endowed Professorship in Germany in 2006, while he remains as an Adjunct Faculty of the Program at CCHMC. Dr. Baum is now the Division Head of Experimental Hematology in Hannover and continues to function as an Adjunct Faculty at CCHMC. Dr. Punam Malik has joined as the Program Leader at the end of 2006.
Program Theme
Develop novel genetic, molecular and cell therapy approaches and delivery systems to treat inherited genetic disorders, and utilize genetic and molecular delivery to study disease pathophysiology.
Program Focus
The Molecular and Gene Therapy Program focuses on developing genetic approaches to treat inherited genetic diseases and cancer, use gene delivery to study disease pathophysiology, develop novel stable gene delivery vectors, and study safety of permanent gene delivery into cells, with the goal of facilitating translation of gene therapy research into clinical trials.
Vector Genotoxicity Studies
Stem and Progenitor Cell Expansion and Selection
Drs. Milsom, Jerabek-Willemsen and Rattman are working on stem cell selection using MGMT.
Fanconi Anemia Studies
Hemoglobinopathies
Program Highlights
I. Vector Genotoxicity Studies
The Molecular and Gene Therapy program investigators have led the field in finding out the molecular mechanisms involved in the events that led to the development of gene therapy-related leukemia in the French X-SCID trial.
Drs. Gerlinde Layh-Schmitt, Anjali Sharma and Kristoffer Weber from the Kalle and Baum Lab are working on Vector Genotoxicity in stem cells.
Dr. Christopher Baum and Dr. Kalle have made key contributions in the field of stem cell genotoxicity of retroviral vectors. Dr. Kalle has done the critical integration site analysis in the French X-SCID trial, the US ADA trial, and the German CGD trial. Dr. Baum has made seminal observations of gene therapy related leukemia in mice and has subsequently gone on to develop sensitive in vitro assays for studying vector genotoxicity. This work has led to several high profile publications (see publications) Dr. Williams, Baum, von Kalle and Malik have been invited to write commentaries and reviews in the field of gene therapy and vector genotoxicity. This has resulted in the development of safer, self inactivating retroviral vectors and lentiviral vectors by Drs. Baum, Williams and Malik. In addition, these studies have had a major national and international impact on the field. Drs. Kalle and Baum have been asked to provide expert recommendations to the Food and Drug Administration (FDA), the National Institutes of Health Recombinant DNA Advisory Committee (RAC). The Translational Trial Development and Support Laboratory (TTDSL), that supports preclinical and clinical gene therapy trials, have been contracted to provide unique services related analysis of vector integration sites in human DNA samples and is leading the pilot on the National Toxicity Protocol for the FDA starting March 2007.
Dr. Baum's group has recently developed an in vitro assay using primary murine hematopoietic progenitor cells to test genotoxicity of retroviral vectors and shown their transformation with retroviral vectors. This has led to testing of vector designs in this model and development of safer vectors. One such self inactivating retroviral vector is now being developed for a clinical trial for X-SCID.
II. Disease Specific Studies
Stem and Progenitor Cell Expansion and Selection
Drs. Williams and Moritz have made major contributions to the field in stem and progenitor selection in vivo with vectors carrying drug selectable markers (reference publications). A hematopoietic stem cell selection trial in patients receiving chemotherapy for gliomas is underway at Cincinnati Children's and will soon be extended to adults in the OSU Cancer Center.
Fanconi Anemia
Another major area of interest is Fanconi Anemia (FA), which is largely led by Dr. Williams, co-leader of the Fanconi Anemia Comprehensive Care Center (FACCC) at Cincinnati Children's and initiated a gene therapy trial for FA. Cells from patients with FA (and cell lines derived from them) undergo G2M arrest upon exposure to genotoxic stress. Dr. Williams has developed retroviral vectors (gamma-retroviral and lentiviral vectors) carrying different FA genes. When FA cell lines are complemented with the retrovirus carrying the specific missing FA gene, the G2M arrest is reversed. Retrovirus mediated complementation of all known Fanconi Anemia subtypes is now a CLIA/CAP certified Clinical Test used to diagnose the specific FA subtype. Cincinnati Children's is the international referral center for the Diagnosis of the FA subtypes using this assay. In the process of translating gene therapy of Fanconi Anemia to patients, Drs. Kelly and Williams have characterized the difficulties in collecting and transducing hematopoietic stem cells from patients with Fanconi Anemia.
Hemoglobinopathies
Dr. Punam Malik has recently joined the Division of Experimental Hematology as the Program Leader. She is an expert in lentiviral vectors and focuses on gene therapy for red blood cell disorders. She has developed novel in vitro and in vivo models of human erythropoiesis that recapitulate globin ontogeny and disease pathophysiology seen in vivo. Her laboratory has also focused on lentiviral vector design for consistent optimal expression of transgenes in erythroid cells for safe and efficacious gene transfer. Using these models, her laboratory has shown phenotypic correction of human beta thalassemia major. Preclinical studies are underway for a clinical trial in beta thalassemia major.
Dr. Malik's laboratory, that focuses on hemoglobinopathies, has now relocated to CCHMC.
Mucopolysaccharoidosis
Dr. Darren Wang from the Pan lab works on gene therapy for MPS.
Dr. Dao Pan is interested in gene therapy for mucopolysacharoidosis. She has been using lentiviral vector delivery in situ and has shown sustenance of gene marked cells following in situ delivery in secondary mice.
Fetal Gene Delivery
Dr. Tim Crombleholme is the head of Fetal Surgery and is interested in gene delivery into lung and placenta. He has successfully used adenoviral vectors and lentiviral vectors to deliver genes into fetal lungs and trachea.
Gene Therapy for Cancer
Dr. Tim Cripe in collaboration with Dr. Antonio Chiocca Ohio State University Comprehensive Cancer Center(OSUCCC) has demonstrated that many pediatric solid tumors are relatively resistant to adenovirus infection due to lack of virus receptors, but are highly susceptible to oncolytic herpes virus 1 (HSV1) infection. Dr. Cripe is testing oncolytic herpes virus vectors for gene therapy of pediatric solid tumors, including neuroblastomas and refractory sarcomas. Ongoing NCI funded investigations include the study of systemic virus and immune response for metastatic disease, the use of viruses in combination with other molecularly targeted therapies, and the development of viruses armed with therapeutic transgenes
III. Gene Therapy Clinical Trials
One of the major focus of the MGT Program has been the development of gene transfer technology for use in therapeutic applications. Dr. David Williams has initiated several gene therapy trials at Cincinnati Children's.
Active Trials
- Gene Therapy for Fanconi Anemia using gamma retroviral vectors. This trial was initiated by Drs. David Williams and Patick Kelly in 2004.
- Hematopoietic stem cell chemoprotection using MGMTP140K during high risk glioma therapy started in summer of 2006, by Drs. David Williams and Lars Wagner; provision of 6-BG by CTEP and GMP grade vector in a collaboration with Dr. Brian Sorrentino at St. Judes Hospital. This trial is being extended to adults via affiliation agreement with OSUCCC (Dr. Rob Caviliere).
Trials in development
- Recombinant oncolytic HSV1 (rRp450) Dr. Tim Cripe has been approved for clinical trial production by the NGVL. Direct intratumoral injection of HSV1716 in adolescents and young adults with refractory sarcomas and neuroblastoma: Dr. Cripe. A second HSV vector has reached clinical trial development. HSV1716 is deleted for the RL1 "neurovirulence" gene (encoding ICP34.5), and is in clinical trials for CNS tumors in Europe under the sponsorship of Crusade Laboratories, Ltd. Dr. Tim Cripe's group has proposed a phase 1 study using direct intratumoral injection of HSV1716 in adolescents and young adults with refractory sarcomas and neuroblastoma. The trial would also represent the first clinical trial of HSV1716 in the United States, the first trial of any HSV-based oncolytic vector for childhood cancers, and the first to include adolescent subjects.
- Gene Therapy for X-SCID using a SIN MLV vector driven by a cellular promoter (Drs. Williams and Baum) with Dr. Adrian Thrasher (London). Preclinical Studies were done jointly by these centers and Dr. Baum. Vector for this trial is being made at Cincinnati Children's. The production of the clinical grade vector is currently scheduled for the Cincinnati Children's vector production facility VPF later this year.
- Gene Therapy for b-thalassemia using SIN lentiviral vectors (Dr. Malik). The vector for this trial will be made at Cincinnati Children's vector production facility. The Cincinnati Children's MGT program and vector production facility has produced GMP grade vector for four clinical trials in the short period of its inception.
IV. Awards and Honors received by the Molecular and Gene Therapy Program Members
Dr. Kalle received the Outstanding New Investigator Award from the American Society of Gene Therapy in 2003.
Drs. Kalle and Baum both received the Langen Award of the Paul Ehrlich Institute in 2006.
Dr. Baum received the Sir Hans Kreb Publication Award for his contribution published in Science in 2005.
Dr. Malik received the Outstanding New Investigator Award from the American Society of Gene Therapy in 2006.
Dr. Williams received several honors and awards:
Member, Institute of Medicine, National Academy of Sciences.
The Frank Oski Award from the American Society of Pediatric Hematology/Oncology in 2006
The Donald Metcalf Award from the International Society of Experimental Hematology in 2006
He continues to serve as Editor-in-Chief of Molecular Therapy, the top-rated journal in the area of gene and molecular therapy.
Scientific Interactions
Programmatic
The Molecular and Gene Therapy Program holds a weekly Molecular and Gene Therapy Translational Meeting jointly with TTDSL and a monthly Vector Club. The Program members closely interact and collaborate with investigators in the Stem Cell Biology, Cell Signaling, Leukemia Biology and Cancer Biology Programs, and participate in shared common meetings, such as EH floor rounds, Journal Club and Saturday Science and Schnecken rounds.
Divisional
Like all other Programs in Experimental Hematology, the Molecular and Gene Therapy program integrates basic, translational and clinical research with the clinical programs in the Division of Hematology-Oncology (HO and closely interacts and collaborates closely with the faculty in HO. The basic and translational research in Fanconi Anemia is translated to clinical research and provides comprehensive care to FA patients in the FACCC. The Comprehensive Sickle Cell Center, Directed by Dr. Joiner in Hematology-Oncology, uses gene transfer methodologies to study the pathophysiology or treat sickle cell disease. Dr. Cripe is a faculty in HO who works on oncolytic HSV-mediated gene therapy for metastatic neuroblastomas and soft tissue sarcomas. The Program participates in the translational research retreats jointly organized by EH and HO and most faculty in the Molecular and Gene Therapy Program provide clinical care in the division of HO.
National and International
The program also has national and international collaborations with the Ohio State Univiersity Cancer Center. Dr. Williams and Dr. John Perentesis co-lead the Pediatric Oncology Program [POP, which represents Columbus Children's Hospital (CCH), Cincinnati Children's and Ohio State University comprehensive cancer center (OSUCCC)]. POP has allowed importation of ongoing pediatric MGMT trial from Cincinnati Children's to adult populations at OSUCCC and diffusion of technology from CCH in AAV vectors to both Cincinnati Children's and OSUCCC and clinical grade AAV vector production at Cincinnati Children's
Experimental Hematology and Molecular and Gene Therapy Program has co-hosted three Stem Cell Clonality and Genotoxicity Retreats. Drs. Baum and Williams have also organized Transatlantic Gene Therapy Retreats (Eberbach, Germany and Baltimore). The third is planned by Williams and Thrasher, funded by Leukemia Lymphoma Society and scheduled for London in 2007.
Core Support and Utilization
Dr. Jose Cancelas, Director of
Research of Hoxworth Blood Center
and Director of the Flow Cytometry
Core, oversees and is seen here
with Erin Kaiser from TTDSL.
The Program heavily utilizes the core facilities
Key Publications
- Yanez-Munoz RJ, Balaggan KS, MacNeil A, Howe SJ, Schmidt M, Smith AJ, Buch P, MacLaren RE, Anderson PN, Barker SE, Duran Y, Bartholomae C, von Kalle C, Heckenlively JR, Kinnon C, Ali RR, Thrasher AJ. Effective gene therapy with non-integrating lentiviral vectors. Nat Med. 2006 Mar;12(3):348-53.
- Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U, Glimm H, Kuhlcke K, Schilz A, Kunkel H, Naundorf S, Brinkmann A, Deichmann A, Fischer M, Ball C, Pilz I, Dunbar C, Du Y, Jenkins NA, Copeland NG, Luthi U, Hassan M, Thrasher AJ, Hoelzer D, von Kalle C, Seger R, Grez M. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EV11, PRDM16 or SETBP1. Nat Med. 2006 Apr; 12((4):401-9.
- Hajitou A, Trepel M, Lilley CE, Soghomonyan S, Alauddin MM, Marini FC 3rd, Restel BH, Ozawa MG, Moya CA, Rangel R, Sun Y, Zaoui K, Schmidt M, von Kalle C, Weitzman MD, Gelovani JG, Pasqualini R, Arap W. A hybrid vector for ligand-directed tumor targeting and molecular imaging. Cell 2006 April 21;125(2):385-98.
- Woods NB, Bottero V, Schmidt M, von Kalle C, Verma IM. Gene therapy: therapeutic gene causing lymphoma. Nature. 2006 Apr 27;440(7088):1123.
- Rattmann I, Kleff V, Sorg UR, Bardenheuer W, Brueckner A, Hilger RA, Opalka B, Seeber S, Flasshove M, Moritz T. Gene transfer of cytidine deaminase protects myelopoiesis from cytidine analogs in an in vivo murine transplant model. Blood. 2006 Nov 1;108(9):2965-71.
- Worsham DN, Schuesler T, von Kalle C, Pan D. In vivo gene transfer into adult stem cells in unconditioned mice by in situ delivery of a lentiviral vector. Mol Ther. 2006 Oct;14(4):514-24.
- Schambach A, Bohne J, Chandra S, Will E, Margison GP, Williams DA, Baum C. Equal potency of gammaretroviral and lentiviral SIN vectors for expression of O6-methylguanine-DNA methyltransferase in hematopoietic cells. Mol Ther. 2006 Feb;13(2):391-400.
- Kustikova O, Fehse B, Modlich U, Yang M, Dullmann J, Kamino K, von Neuhoff N, Schlegelberger B, Li Z, Baum C. Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science. 2005 May 20;308(5725):1171-4.
- Schmidt M, Hacein-Bey-Abina S, Wissler M, Carlir F, Lim A, Prinz C, Glimm H, Andre-Schmutz I, Hue C, Garrigue A, Le Deist F, Lagresle C, Fischer A, Cavazzana-Calvo M, von Kalle C. Clonal Evidence for the Transduction of CD34+ Cells with Lymphomyeloid Differentiation Potential and Self-Renewal Capacity in the SCID-XI Gene Therapy Trial. Blood. 2005 Apr 1;105(7):2699-706.
- Fischer A, Abina SH, Thrasher A, von Kalle C, Cavazzana-Calvo M. LMO2 and gene therapy for severe combined immunodeficiency. N Engl J Med. 2004 June 10; 350(24):2526-7; author reply 2526-7.
- Galla M, Will E, Kraunus J, Chen L, Baum C. Retroviral pseudotransduction for targeted cell manipulation. Mol Cell. 2004 Oct 22;16(2):309-15.
- Puthenveetil G, Scholes J, Carbonell D, Qureshi N, Xia P, Zeng L, Li S, Yu Y, Hiti AL, Yee JK, Malik P. Successful correction of the human beta-thalassemia major phenotype using a lentiviral vector. Blood. 2004 Dec 1;104(12):3445-53.
- Mohamedali A, Xia P Richard E, Moreau-Gaudry F and Malik P. Self-Inactivating Lentiviral Vectors Express Long-Term, Resist Proviral Methylation but do not Confer Position-Independent Expression. In press citation, Molecular Therapy, 10(2): 249-59, 2004.
- Sena-Esteves M, Tebbets JC, Steffens S, Crombleholme T, Flake AW. Optimized large-scale production of high titer lentivirus vector pseudotypes. J Virol Methods. 2004 122(2):131-9.
- Gaspar HB, Parsley KL, Howe S, King D, Gilmour KC, Sinclair J, Brouns G, Schmidt M, von Kalle C, Barington T, Jakobsen MA, Christensen HO, Al Ghonaium A, White HN, Smith JL, Levinsky RJ, Ali RR, Kinnon C, Thrasher AJ. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Lancet. 2004 Dec 18;364(9452):2181-7.
- Neff T, Horn PA, Peterson LJ, Thomasson BM, Thompson J, Williams DA, Schmidt M, Georges GE, von Kalle C, Kiem HP. Methylguanine methyltransferase-mediated in vivo selection and chemoprotection of allogeneic stem cells in a large-animal model. J Clin Invest. 2003 Nov;112(10):1581-8.
- Schmidt M, Carbonaro DA, Speckmann C, Wissler M, Bohnsack J, Elder M, Aronow BJ, Nolta JA, Kohn DB, von Kalle C. Clonality analysis after retroviral-mediated gene transfer to CD34+ cells from the cord blood of ADA-deficient SCID neonates. Nat Med 2003 Apr;9(4):463-8.
- Hacein-Bey-Abina S*, von Kalle C*, (cofirst author*) Schmidt M*, McCormack MP, Wulffraat N, Leboulch P, Lim A, Osborne CS, Pawliuk R, Morillon E, Sorensen R, Forster A, Fraser P, Cohen JI, de Saint Basile G, Alexander I, Wintergerst U, Frebourg T, Aurias A, Stoppa-Lyonnet D, Romana S, Radford-Weiss I, Gross F, Valensi F, Delabesse E, Macintyre E, Sigaux F, Soulier J, Leiva LE, Wissler M, Prinz C, Rabbitts TH, Le Deist F, Fischer A, Cavazzana-Calvo M. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003 Oct 17;302(5644):415-9.
- Lim FY, Kobinger GP, Weiner DJ, Radu A, Wilson JM, Crombleholme TM. Human fetal trachea-SCID mouse xenografts: efficacy of vesicular stomatitis virus-G pseudotyped lentiviral-mediated gene transfer. J Pediatr Surg. 2003 Jun;38(6):834-9.
Invited Reviews and Commentaries in the Last 5 Years
- Williams DA. ASGT Advises NIH on Funding of Gene Therapy Trials. Mol Ther. 2007
- Cheng JC, Sakamoto KM, Horwitz EM, Karsten SL, Shoemaker L, Kornblum HI, Malik P. A Meeting Report: "New Technologies in Stem Cell Research" Stem Cells. 2007
- Baum C, Schambach A, Bohne J, Galla M. Retrovirus vectors: toward the plentivirus? Mol Ther. 2006
- Williams DA. NIH funding of gene therapy trials. Mol Ther. 2006
- Williams DA. Vector insertion, mutagenesis and transgene toxicity. Mol Ther. 2006
- Williams DA. Gene therapy advances but struggles to interpret safety data in small animal models. Mol Ther. 2006
- Baum C, Kustikova O, Modlich U, Li Z, Fehse B. Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors. Hum Gene Ther. 2006.
- Williams DA, Croop J, Kelly P. Gene therapy in the treatment of Fanconi anemia, a progressive bone marrow failure syndrome. Curr Opin Mol Ther. 2005
- Williams DA, Cripe TP. Adventitious mutations in clinical grade vectors: an issue to consider? Mol Ther. 2006
- Madigan C, Malik P. Pathophysiology and therapy for haemoglobinopathies; Part I: sickle cell disease. Expert Rev Mol Med. 2006
- Urbinati F, Madigan C, Malik P. Pathophysiology and therapy for haemoglobinopathies; Part II: thalassaemias. Expert Rev Mol Med. 2006
- Williams DA. An emerging consensus on recommendations to facilitate clinical gene transfer. Mol Ther. 2006
- Williams DA. New AAV serotypes may broaden the therapeutic pipeline to human gene therapy. Mol Ther. 2006
- Klump H, Schiedlmeier B, Baum C. Control of self-renewal and differentiation of hematopoietic stem cells: HOXB4 on the threshold. Ann N Y Acad Sci. 2005
- von Kalle C, Fehse B, Layh-Schmitt G, Schmidt M, Kelly P, Baum C. Stem cell clonality and genotoxicity in hematopoietic cells: gene activation side effects should be avoidable. Semin Hematol. 2004.
- Williams DA. FDA guidance document on monitoring delayed adverse events a good first start. Mol Ther. 2005
- Cripe TP, Thomson B, Boat TF, Williams DA. Promoting translational research in academic health centers: navigating the "roadmap". Acad Med. 2005.
- Malik P, Arumugam PI, Yee JK, Puthenveetil G. Successful correction of the human Cooley's anemia beta-thalassemia major phenotype using a lentiviral vector flanked by the chicken hypersensitive site 4 chromatin insulator. Ann N Y Acad Sci. 2005
- Malik P, Arumugam PI. Gene Therapy for {beta}-Thalassemia. Hematology Am Soc Hematol Educ Program. 2005;:45-50.
- Williams DA, Croop J, Kelly P. Gene therapy in the treatment of Fanconi anemia, a progressive bone marrow failure syndrome. Curr Opin Mol Ther. 2005 Oct;7(5):461-6.
- Williams DA. The NIH roadmap: timing is everything. Mol Ther. 2005
- Li Z, Modlich U, Baum C. Safety and efficacy in retrovirally modified haematopoietic cell therapy. Best Pract Res Clin Haematol. 2004.
- Fehse B, Kustikova OS, Bubenheim M, Baum C. Pois(s)on--it's a question of dose...Gene Ther. 2004.
- von Kalle C, Baum C, Williams DA. Lenti in red: progress in gene therapy for human hemoglobinopathies. J Clin Invest. 2004
- Klein C, Baum C. Gene therapy for inherited disorders of haematopoietic cells. Hematol J. 2004.
- Baum C, von Kalle C, Staal FJ, Li Z, Fehse B, Schmidt M, Weerkamp F, Karlsson S, Wagemaker G, Williams DA. Chance or necessity? Insertional mutagenesis in gene therapy and its consequences. Mol Ther. 2004.
- Puthenveetil G, Malik P. Gene therapy for hemoglobinopathies: are we there yet? Curr Hematol Rep. 2004
- Keswani SG, Crombleholme TM. Gene transfer to the tracheobronchial tree: implications for fetal gene therapy for cystic fibrosis. Semin Pediatr Surg. 2004
- Malik P. Gene Therapy for hemoglobinopathies: new models, new approaches. Blood, 2003.
- Baum C, Fehse B. Mutagenesis by retroviral transgene insertion: risk assessment and potential alternatives. Curr Opin Mol Ther. 2003
- Baum C, von Kalle C. Gene therapy targeting hematopoietic cells: better not leave it to chance. Acta Haematol. 2003.
- Schmidt M, Glimm H, Wissler M, Hoffmann G, Olsson K, Sellers S, Carbonaro D, Tisdale JF, Leurs C, Hanenberg H, Dunbar CE, Kiem HP, Karlsson S, Kohn DB, Williams DA, Von Kalle C: Efficient characterization of retro-, lenti-, and foamyvector-transduced cell populations by high-accuracy insertion site sequencing. Annals of the New York Academy of Sciences. 2003 May;996:112-21.
- Baum C, Dullmann J, Li Z, Fehse B, Meyer J, Williams DA, von Kalle C. Side effects of retroviral gene transfer into hematopoietic stem cells. Blood. 2003.
- Shi PA, Hematti P, von Kalle C, Dunbar CE. Genetic marking as an approach to studying in vivo hematopoiesis: progress in the non-human primate model. Oncogene. 2002.
Related Links
For further information regarding the Molecular and Gene Therapy program, please contact Dr. Punam Malik at 513-636-1333. For additional information about the Division of Experimental Hematology, please contact Dr. David Williams at 513-636-0364. The Division of Experimental Hematology can be found in Room 6529 of Location R (Research Foundation Building).
