Golam Mohi

Education

  • PhD, University of Tokyo
  • Postdoc, Harvard Medical School

Primary Appointment

  • Professor, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

Cell signaling, hematopoietic stem cell biology, molecular and epigenetic mechanisms of leukemia.

Research Description

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, is activated in response to a variety of cytokines. A somatic JAK2V617F mutation has been found in a majority of patients with myeloproliferative neoplasms (MPNs). One of the major interests in our lab is to study the role of the JAK/STAT signaling in the pathogenesis of MPNs. We are also investigating the interaction of epigenetic modulators with the JAK2 mutation in MPNs using state-of-the-art techniques and genetically engineered animal models.

Current research projects in my laboratory are focused in the following areas:

(1) Elucidation of the role of JAK2 and JAK2V617F mutation in hematopoiesis and myeloproliferative neoplasms (MPNs).

(2) Investigation of the role of SHP2 in MPNs, and targeting of SHP2 in MPNs using SHP2-specific inhibitors.

(3) Investigation of the role of protein tyrosine phosphatase PTPN1 in myeloid neoplasms.

(4) Investigation of the role of histone methyltransferase EZH2 in the pathogenesis of myelofibrosis (MF).

(5) Testing the efficacy of potential new targeted therapies for MPNs using novel animal models.

Selected Publications

  • Dutta A, Hutchison R, Mohi G. Hmga2 promotes the development of myelofibrosis in Jak2(V617F) knockin mice by enhancing TGF-β1 and Cxcl12 pathways. Blood. 2017;130(7): 920-932. PMID: 28637665 | PMCID: PMC5561898
  • Jobe F, Patel B, Kuzmanovic T, Makishima H, Yang Y, Przychodzen B, Hutchison R, Bence K, Maciejewski J, Mohi G. Deletion of Ptpn1 induces myeloproliferative neoplasm. Leukemia. 2017;31(5): 1229-1234. PMID: 28111468
  • Dutta A, Yan D, Hutchison R, Mohi G. STAT3 mutations are not sufficient to induce large granular lymphocytic leukaemia in mice. British journal of haematology. 2016. PMID: 28025836 | PMCID: PMC5484756
  • Gu S, Chan W, Mohi G, Rosenbaum J, Sayad A, Lu Z, Virtanen C, Li S, Neel B, Van Etten R. Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1. Blood. 2016;127(14): 1803-13. PMID: 26773044 | PMCID: PMC4825414
  • Yang Y, Akada H, Nath D, Hutchison R, 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 | PMCID: PMC4929929
  • Yan D, Jobe F, Hutchison R, 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 | PMCID: PMC4598256
  • Akada H, Akada S, Hutchison R, Mohi G. Loss of wild-type Jak2 allele enhances myeloid cell expansion and accelerates myelofibrosis in Jak2V617F knock-in mice. Leukemia. 2014;28(8): 1627-35. PMID: 24480985 | PMCID: PMC4117831
  • Akada H, Akada S, Hutchison R, Sakamoto K, Wagner K, Mohi G. Critical role of Jak2 in the maintenance and function of adult hematopoietic stem cells. Stem cells (Dayton, Ohio). 2014;32(7): 1878-89. PMID: 24677703 | PMCID: PMC4063883
  • Akada H, Akada S, Gajra A, Bair A, Graziano S, Hutchison R, Mohi G. Efficacy of vorinostat in a murine model of polycythemia vera. Blood. 2012;119(16): 3779-89. PMID: 22408262 | PMCID: PMC3335382
  • Akada H, Akada S, Hutchison R, 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 | PMCID: PMC3436240
  • Yan D, Hutchison R, 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 | PMCID: PMC3433092
  • Yan D, Hutchison R, Mohi G. Critical requirement for Stat5 in a mouse model of polycythemia vera. Blood. 2011;119(15): 3539-49. PMID: 22144185 | PMCID: PMC3325041
  • Zou H, Yan D, Mohi G. Differential biological activity of disease-associated JAK2 mutants. FEBS letters. 2011;585(7): 1007-13. PMID: 21362419 | PMCID: PMC3070755
  • Akada H, Yan D, Zou H, Fiering S, Hutchison R, Mohi M. 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 | PMCID: PMC2867267
  • Mohi M, Neel B. The role of Shp2 (PTPN11) in cancer. Current opinion in genetics & development. 2007;17(1): 23-30. PMID: 17227708
  • Mohi M, Williams I, Dearolf C, Chan G, Kutok J, Cohen S, Morgan K, Boulton C, Shigematsu H, Keilhack H, Akashi K, Gilliland D, Neel B. 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
  • Araki T, Mohi M, Ismat F, Bronson R, Williams I, Kutok J, Yang W, Pao L, Gilliland D, Epstein J, Neel B. Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nature medicine. 2004;10(8): 849-57. PMID: 15273746
  • Mohi M, Boulton C, Gu T, Sternberg D, Neuberg D, Griffin J, Gilliland D, Neel B. Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(9): 3130-5. PMID: 14976243 | PMCID: PMC365755
  • Sattler M, Mohi M, Pride Y, Quinnan L, Malouf N, Podar K, Gesbert F, Iwasaki H, Li S, Van Etten R, Gu H, Griffin J, Neel B. Critical role for Gab2 in transformation by BCR/ABL. Cancer cell. 2002;1(5): 479-92. PMID: 12124177