Golam Mohi, PhD

Current Appointments

• Associate Professor of Pharmacology

Hospital Campus

• Downtown

Education & Fellowships

• Postdoctoral Fellow: Harvard Medical School, 2005, Cancer Biology
• PhD: University of Tokyo, 2001, Molecular and Cell Biology

Associations/Memberships

• American Society of Hematology (ASH)
• American Association for Cancer Research (AACR)

Publications

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Research Abstract

Hematopoiesis is an important biological process in which small numbers of self-renewing hematopoietic stem cells (HSC) generate large numbers of mature blood cells of multiple distinct lineages. This orderly process is regulated by signal transduction cascades mediated by cytokines and their receptors, and requires appropriate balance of cell proliferation, differentiation, adhesion, migration, survival and death. Abnormal regulation of this process can cause myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) or leukemia. Understanding the signaling pathways that regulate the normal hematopoiesis, and determining how these signaling pathways are deranged in diseases is important for the rational development of new therapies for blood diseases.

Many hematopoietic signaling pathways are controlled by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). JAK2, a member of the Janus family of non-receptor PTKs, is activated in response to a variety of cytokines. A Somatic mutation (V617F) in JAK2 has been found in a majority of patients with myeloproliferative neoplasms (MPN) including 95% cases of polycythemia vera (PV) and 50-60% cases of essential thrombocythemia (ET) and primary myelofibrosis (PMF). The long-term goals of my laboratory are to elucidate the role of the JAK/STAT pathway in normal hematopoiesis and hematologic diseases. We are using molecular and cell biology, genetic and biochemical approaches to accomplish these goals. We have generated tissue-specific knock-out and knock-in mice models to define the role of the JAK/STAT pathway in the maintenance and function of hematopoietic stem cells and in the pathogenesis of myeloid neoplasms/leukemias. We are also using these mice models to test novel therapies for myeloid neoplasms/leukemias. 

Selected Publications

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 Jun;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 Mar 2;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 Aug;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 Feb;7(2):179-91. PMID: 15710330

Ren SY, Bolton E, Mohi MG, Morrione A, Neel BG, Skorski T. Phosphatidylinositol 3-kinase p85{alpha} subunit-dependent interaction with BCR/ABL-related fusion tyrosine kinases: molecular mechanisms and biological consequences. Mol Cell Biol. 2005 Sep;25(18):8001-8. PMID: 16135792

Masiello D*, Mohi MG*, McKnight NC, Smith B, Neel BG, Balk SP, Bubley GJ. Combining an mTOR antagonist and receptor tyrosine kinase inhibitors for the treatment of prostate cancer. Cancer Biol Ther. 2007 Feb;6(2):195-201. PMID: 17218776 (*Co-first author).

Mohi MG, Neel BG. The role of Shp2 (PTPN11) in cancer. Curr Opin Genet Dev. 2007 Feb;17(1):23-30. Review. 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 Apr 30;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 Apr 29;115(17):3589-97. PMID: 20197548

Zou H, Yan D, Mohi G. Differential biological activity of disease-associated JAK2 mutants. FEBS Lett. 2011 Apr 6;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 Apr 12;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 Apr 19;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 Feb 27. [Epub ahead of print]; 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 Aug 30;120(9):1888-98. PMID: 22837531