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Asish K Ghosh

TitleProf,Asoc
InstitutionUniversity of Oklahoma Health Sciences Center
DepartmentStephenson Cancer Center
Phone405/271-1387
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    Collapse Overview 
    Collapse overview
    B cell chronic lymphocytic leukemia (CLL) is a devastating, incurable B-cell malignancy and the most common form of leukemia in the Western Hemisphere.

    The research of Asish K. Ghosh, Ph.D., primarily focuses on
    • Extracellular vesicles and tumor microenvironment
    • CLL B cell/bone marrow stromal cell crosstalk
    • Role of extracellular vesicles in CLL progression and therapeutic outcomes
    • CLL B cell biology and drug targeting
    • Receptor tyrosine kinase signaling in CLL B-cells (Pre-/post-therapy)
    • Regulation of leukemic B-cell growth

    Dr. Ghosh has a particular interest in identifying therapeutic and prognostic factors to better predict clinical progression of CLL and therapeutic outcome.

    Recently, Dr. Ghosh and his team identified a novel receptor tyrosine kinase called Axl in CLL B cells, which seems to play a critical role in CLL B-cell survival and apoptotic resistance. Interestingly, targeted inhibition of Axl induces massive cell death in primary CLL B cells from CLL patients, suggesting that it may have potential for future use as a therapeutic agent, either alone or in combination with the chemotherapeutic agents commonly being used to treat CLL.

    Dr. Ghosh's laboratory has been working extensively to pursue the role of circulating microvesicles and exosomes in human malignancies, particularly CLL. His team has found these extracellular vesicles have a unique role — they function as a mediator of communication between the malignant tumor cells and cells at the distant tissues, such as bone marrow stroma.

    Dr. Ghosh's research also focuses on further characterization of these circulating extracellular vesicles to be used as predictors of the clinical course and therapeutic outcome in CLL.

    Focus areas
    • In-depth study of the intracellular cell survival signaling pathways in CLL B cells
    • Implications of receptor tyrosine kinase-mediated signal transmission in cell survival and apoptosis resistance
    • Targeting potential therapeutic components in vitro and in vivo
    • Testing of potential therapeutic agents in primary CLL cell culture systems
    • Isolation and characterization of circulating microvesicles and exosomes from CLL plasma and purified CLL cells in vitro
    • Functional interaction of circulating microvesicles and exosomes with the CLL bone marrow stromal cells to modulate the CLL tumor microenvironment
    • Generation of microvesicles and exosomes as a result of interaction of the leukemic B cells with other cell types in the CLL tumor microenvironment
    • Studying aberrant intracellular signaling pathways in CLL bone marrow stromal cells

    Significance to patient care
    CLL accounts for about 11 percent of all newly diagnosed hematologic neoplasms. Given its chronic nature, there are estimated to be about 150,000 people in the U.S. who are living with CLL.
    Importantly, clinicians are now able to more effectively treat progressive CLL, but treatment options are much less effective when a patient relapses. Since CLL patients are not routinely cured, clinicians are frequently faced with second line therapies that have very inferior levels of deep clinical response and durability.
    In addition, the current therapies for upfront treatments use agents that are either toxic to the marrow or difficult to use in older patients (those age 65 and older). Therefore, any insights into drugs that have unique mechanisms of action and are nontoxic to the bone marrow are desperately needed.
    Identification of unique therapeutic targets in CLL requires more in-depth study of the leukemic B-cell biology and signaling pathways.

    Professional highlights
    • Fellowships from the Council of Scientific and Industrial Research (CSIR), Government of India – 1990 - 2005
    • Young Investigator Award in 2008 at the Mayo Clinic Angiogenesis Symposium
    • Recipient of the First Hematology Research Summit AWARD at Mayo Clinic - 2012
    • Recipient of the Eagles Cancer Research Award - 2012-2013
    • Member of the ASH Scientific Committee on Lymphoid Neoplasia – 2013
    • Member of the Graduate Program in Biomedical Sciences (GPiBS) Committee, University of Oklahoma: 2016 (3-year term)

    Collapse Research 
    Collapse research activities and funding
         (Asish K Ghosh)Oct 1, 2018 - Sep 30, 2019
    PHF Bridge Fund
    Targeting Kinase Network in B Cell Chronic Lymphocytic Leukemia
    Role Description: Focus of this grant is to define the AXL signaling network in CLL B-cells. We will also define if the AXL signaling axis is a valid target in CLL therapy
    Role: Principal Investigator

    R01CA170006     (GHOSH, ASISH KUMAR)Aug 1, 2013 - May 31, 2018
    NIH/NCI
    Microvesicle Dynamics in B-Cell Chronic Lymphocytic Leukemia Tumor Microenvironme
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Sinha S, Boysen JC, Chaffee KG, Kabat BF, Slager SL, Parikh SA, Secreto CR, Call T, Shanafelt TD, Leis JF, Warner SL, Bearss DJ, Ghosh AK, Kay NE. Chronic lymphocytic leukemia cells from ibrutinib treated patients are sensitive to Axl receptor tyrosine kinase inhibitor therapy. Oncotarget. 2018 Dec 14; 9(98):37173-37184. PMID: 30647852.
      View in: PubMed
    2. Maiti GP, Kay NE, Ghosh AK. Microvesicles in CLL: predictor of disease progression/relapse. Oncotarget. 2017 Oct 31; 8(53):90632-90633. PMID: 29207590.
      View in: PubMed
    3. Boysen J, Nelson M, Magzoub G, Maiti GP, Sinha S, Goswami M, Vesely SK, Shanafelt TD, Kay NE, Ghosh AK. Dynamics of microvesicle generation in B-cell chronic lymphocytic leukemia: implication in disease progression. Leukemia. 2017 02; 31(2):350-360. PMID: 27480387.
      View in: PubMed
    4. Kay NE, Sassoon T, Secreto C, Sinha S, Shanafelt TD, Ghosh AK, Arbiser JL. Tris (dibenzylideneacetone) dipalladium: a small-molecule palladium complex is effective in inducing apoptosis in chronic lymphocytic leukemia B-cells. Leuk Lymphoma. 2016 10; 57(10):2409-16. PMID: 27189785.
      View in: PubMed
    5. Sinha S, Boysen J, Nelson M, Warner SL, Bearss D, Kay NE, Ghosh AK. Axl activates fibroblast growth factor receptor pathway to potentiate survival signals in B-cell chronic lymphocytic leukemia cells. Leukemia. 2016 06; 30(6):1431-6. PMID: 26598018.
      View in: PubMed
    6. Sinha S, Boysen J, Nelson M, Secreto C, Warner SL, Bearss DJ, Lesnick C, Shanafelt TD, Kay NE, Ghosh AK. Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors. Clin Cancer Res. 2015 May 01; 21(9):2115-26. PMID: 25673699.
      View in: PubMed
    7. Boysen J, Sinha S, Price-Troska T, Warner SL, Bearss DJ, Viswanatha D, Shanafelt TD, Kay NE, Ghosh AK. The tumor suppressor axis p53/miR-34a regulates Axl expression in B-cell chronic lymphocytic leukemia: implications for therapy in p53-defective CLL patients. Leukemia. 2014 Feb; 28(2):451-5. PMID: 24217154.
      View in: PubMed
    8. Ferrajoli A, Shanafelt TD, Ivan C, Shimizu M, Rabe KG, Nouraee N, Ikuo M, Ghosh AK, Lerner S, Rassenti LZ, Xiao L, Hu J, Reuben JM, Calin S, You MJ, Manning JT, Wierda WG, Estrov Z, O'Brien S, Kipps TJ, Keating MJ, Kay NE, Calin GA. Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia. Blood. 2013 Sep 12; 122(11):1891-9. PMID: 23821659.
      View in: PubMed
    9. Ghosh AK, Kay NE. Critical signal transduction pathways in CLL. Adv Exp Med Biol. 2013; 792:215-39. PMID: 24014299.
      View in: PubMed
    10. Shanafelt TD, Call TG, Zent CS, Leis JF, LaPlant B, Bowen DA, Roos M, Laumann K, Ghosh AK, Lesnick C, Lee MJ, Yang CS, Jelinek DF, Erlichman C, Kay NE. Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. Cancer. 2013 Jan 15; 119(2):363-70. PMID: 22760587.
      View in: PubMed
    11. Ghosh AK, Secreto C, Boysen J, Sassoon T, Shanafelt TD, Mukhopadhyay D, Kay NE. The novel receptor tyrosine kinase Axl is constitutively active in B-cell chronic lymphocytic leukemia and acts as a docking site of nonreceptor kinases: implications for therapy. Blood. 2011 Feb 10; 117(6):1928-37. PMID: 21135257.
      View in: PubMed
    12. Shanafelt T, Zent C, Byrd J, Erlichman C, Laplant B, Ghosh A, Call T, Villalona-Calero M, Jelinek D, Bowen D, Laumann K, Wu W, Hanson C, Kay N. Phase II trials of single-agent anti-VEGF therapy for patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2010 Dec; 51(12):2222-9. PMID: 21054149.
      View in: PubMed
    13. Ghosh AK, Secreto CR, Knox TR, Ding W, Mukhopadhyay D, Kay NE. Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression. Blood. 2010 Mar 04; 115(9):1755-64. PMID: 20018914.
      View in: PubMed
    14. Sinha S, Dutta S, Datta K, Ghosh AK, Mukhopadhyay D. Von Hippel-Lindau gene product modulates TIS11B expression in renal cell carcinoma: impact on vascular endothelial growth factor expression in hypoxia. J Biol Chem. 2009 Nov 20; 284(47):32610-8. PMID: 19801654.
      View in: PubMed
    15. Ding W, Nowakowski GS, Knox TR, Boysen JC, Maas ML, Schwager SM, Wu W, Wellik LE, Dietz AB, Ghosh AK, Secreto CR, Medina KL, Shanafelt TD, Zent CS, Call TG, Kay NE. Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression. Br J Haematol. 2009 Nov; 147(4):471-83. PMID: 19751240.
      View in: PubMed
    16. Shanafelt TD, Call TG, Zent CS, LaPlant B, Bowen DA, Roos M, Secreto CR, Ghosh AK, Kabat BF, Lee MJ, Yang CS, Jelinek DF, Erlichman C, Kay NE. Phase I trial of daily oral Polyphenon E in patients with asymptomatic Rai stage 0 to II chronic lymphocytic leukemia. J Clin Oncol. 2009 Aug 10; 27(23):3808-14. PMID: 19470922.
      View in: PubMed
    17. Ghosh AK, Shanafelt TD, Cimmino A, Taccioli C, Volinia S, Liu CG, Calin GA, Croce CM, Chan DA, Giaccia AJ, Secreto C, Wellik LE, Lee YK, Mukhopadhyay D, Kay NE. Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells. Blood. 2009 May 28; 113(22):5568-74. PMID: 19336759.
      View in: PubMed
    18. Ghosh AK, Kay NE, Secreto CR, Shanafelt TD. Curcumin inhibits prosurvival pathways in chronic lymphocytic leukemia B cells and may overcome their stromal protection in combination with EGCG. Clin Cancer Res. 2009 Feb 15; 15(4):1250-8. PMID: 19228728.
      View in: PubMed
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