Major Research Areas
Golam Mohi, PhD
- Professor of Pharmacology
Research Programs and Affiliations
- Biomedical Sciences Program
Education & Fellowships
- Postdoctoral Fellow: Harvard Medical School, 2005, Cancer Biology
- PhD: University of Tokyo, 2001, Molecular and Cell Biology
- Stem cell biology, cell signaling, hematopoiesis and blood cancer
- Identification of Potential New Therapies for Myeloproliferative Neoplasms
- American Society of Hematology (ASH)
- American Association for Cancer Research (AACR)
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My laboratory focuses on understanding the molecular and epigenetic mechanisms involved in the regulation of normal hematopoiesis and hematologic malignancies. The ultimate goal of our research is to identify new therapeutic targets and develop novel therapeutic strategies for treatment of leukemia. JAK2, a member of the Janus family of non-receptor protein tyrosine kinases (JAK), is activated in response to a variety of cytokines. A somatic point mutation (V617F) in the JAK2 tyrosine kinase has been found in a majority of patients with myeloproliferative neoplasms (MPNs) including 95% cases of polycythemia vera (PV) and 50-60% cases of essential thrombocythemia (ET) and primary myelofibrosis (PMF). One of the major areas of our research is to define the role of JAK2 and JAK2V617F in hematopoiesis and in the pathogenesis of MPNs. We are utilizing state-of-the-art techniques and genetically engineered mouse models to uncover the mechanisms involved in leukemogenesis.
Current research projects in my laboratory are focused in the following areas:
- Elucidation of the role of JAK2 and JAK2V617F mutation in hematopoiesis and myeloproliferative neoplasms (MPNs).
- Investigation of the role of SHP2 in MPNs, and targeting of SHP2 in MPNs using SHP2-specific inhibitors.
- Investigation of the role of protein tyrosine phosphatase PTPN1 in myeloid neoplasms.
- Investigation of the role of histone methyltransferase EZH2 in the pathogenesis of MF.
- Testing the efficacy of potential new targeted therapies for MPNs using novel animal models.
Sattler M*, Mohi MG*, Pride YB, Quinnan LR, Malouf NA, Podar K, Gesbert F, Iwasaki H, Li S, Van Etten RA, Gu H, Griffin JD, Neel BG. Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell. 2002;1(5):479-92. PMID: 12124177 (*Co-first author).
Mohi MG, Boulton C, Gu TL, Sternberg DW, Neuberg D, Griffin JD, Gilliland DG, Neel BG. Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs. Proc Natl Acad Sci U S A. 2004;101(9):3130-5. PMID: 14976243
Araki T, Mohi MG, Ismat FA, Bronson RT, Williams IR, Kutok JL, Yang W, Pao LI, Gilliland DG, Epstein JA, Neel BG. Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nat Med. 2004;10(8):849-57. PMID: 15273746
Mohi MG, Williams IR, Dearolf CR, Chan G, Kutok JL, Cohen S, Morgan K, Boulton C, Shigematsu H, Keilhack H, Akashi K, Gilliland DG, Neel BG. Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell. 2005;7(2):179-91. PMID: 15710330
Mohi MG, Neel BG. The role of Shp2 (PTPN11) in cancer. Curr Opin Genet Dev. 2007;17(1):23-30. PMID: 17227708
Chan G, Kalaitzidis D, Usenko T, Kutok JL, Yang W, Mohi MG, Neel BG. Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis. Blood. 2009;113(18):4414-24. PMID: 19179468
Akada H, Yan D, Zou H, Fiering S, Hutchison RE, Mohi MG. Conditional expression of heterozygous or homozygous Jak2V617F from its endogenous promoter induces a polycythemia vera-like disease. Blood. 2010;115(17):3589-97. PMID: 20197548
Zou H, Yan D, Mohi G. Differential biological activity of disease-associated JAK2 mutants. FEBS Lett. 2011;585(7):1007-13. PMID: 21362419
Yan D, Hutchison RE, Mohi G. Critical requirement for Stat5 in a mouse model of polycythemia vera. Blood. 2012;119(15):3539-49. PMID: 22144185
Akada H, Akada S, Gajra A, Bair A, Graziano S, Hutchison RE, Mohi G. Efficacy of vorinostat in a murine model of polycythemia vera. Blood. 2012;119(16):3779-89. PMID: 22408262
Akada H, Akada S, Hutchison RE, Mohi G. Erythroid lineage-restricted expression of Jak2V617F is sufficient to induce a myeloproliferative disease in mice. Haematologica. 2012;97(9):1389-93. PMID: 22371173
Yan D, Hutchison RE, Mohi G. Tyrosine 201 is required for constitutive activation of JAK2V617F and efficient induction of myeloproliferative disease in mice. Blood. 2012;120(9):1888-98. PMID: 22837531
Akada H, Akada S, Hutchison RE, Sakamoto K, Wagner KU, Mohi G.Critical role of Jak2 in the maintenance and function of adult hematopoietic stem cells. Stem Cells. 2014;32(7):1878-89. PMID: 24677703
Akada H, Akada S, Hutchison RE, Mohi G.Loss of wild-type Jak2 allele enhances myeloid cell expansion and accelerates myelofibrosis in Jak2V617F knock-in mice. Leukemia. 2014;28:1627-1635. PMID:24480985
Yan D, Jobe F, Hutchison RE, Mohi G. Deletion of Stat3 enhances myeloid cell expansion and increases the severity of myeloproliferative neoplasms in Jak2V617F knock-in mice. Leukemia. 2015; 29(10):2050-61. PMID: 26044284
Gu S*, Chan WW*, Mohi G*, Rosenbaum J, Sayad A, Lu Z, Virtanen C, Li S, Neel BG, Van Etten RA. Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1. Blood. 2016; 127(14):1803-13. PMID: 26773044 (*Co-first author).
Yang Y, Akada H, Nath D, Hutchison RE, Mohi G.Loss of Ezh2 cooperates with Jak2V617F in the development of myelofibrosis in a mouse model of myeloproliferative neoplasm. Blood. 2016; 127(26):3410-23. PMID: 27081096
Dutta A, Yan D, Hutchison RE, Mohi G. STAT3 mutations are not sufficient to induce large granular lymphocytic leukaemia in mice. Br J Haematol. 2016. doi: 10.1111/bjh.14487. [Epub ahead of print]. PMID: 28025836
Jobe F, Patel B, Kuzmanovic T, Makishima H, Yang Y, Przychodzen B, Hutchison RE, Bence KK, Maciejewski JP, Mohi G. Deletion of Ptpn1 induces myeloproliferative neoplasm. Leukemia. 2017. doi: 10.1038/leu.2017.31. [Epub ahead of print]. PMID: 28111468
Complete list of published work in MyBibliography: