SandeepGurbuxani

Sandeep Gurbuxani, MBBS, PhD

Instructor of Pathology

Dr. Sandeep Gurbuxani became interested in the biology of acute lymphoblastic leukemia (ALL) soon after graduating from medical school. He was as a clinical research officer on a multi-center trial set-up in collaboration with the National Cancer Institute. The objective of the study was to initiate a cooperative group trial that would treat children and young adults diagnosed with ALL on a uniform protocol that was standardized and more intensive than protocols being used in India at that time. In addition to improving patient outcome, it was believed that one might identify differences in the biology of the disease when compared to what was known from studies conducted largely in the more industrialized and developed Western countries. While his responsibilities were to document toxicities to therapy and to ensure compliance with the protocol, Dr. Gurbuxani soon became interested in the biology of the disease and was particularly impressed by the phenomenon of resistant disease, and how difficult it was to re-induce patients into remission after relapse. He enrolled in the PhD program of the All India Institute of Medical Sciences, Delhi and studied mechanisms of drug resistance in acute leukemia.

Dr. Gurbuxani’s subsequent post-doctoral fellowship in France focused on the very basic aspects of mechanisms of resistance to chemotherapy-induced cell death. In 2002, he continued his clinical training in Clinical Pathology and pursued a fellowship in Hematopathology in the United States. His current clinical interests cover all areas of hematopathology, and his research is focused on the mechanisms of resistance to chemotherapy-induced cell death in cancer.

Specifically, Dr. Gurbuxani is actively working on the mechanisms of glucocorticoid-induced cell death (and the resistance to this cell death) in ALL. While significant progress has been made in the therapy of childhood ALL, the outcome for adult ALL and relapsed ALL remains poor. Glucocorticoids (GCs) such as dexamethasone and prednisone are the mainstay of ALL therapy. Multiple studies in childhood ALL have demonstrated GC resistance after GC monotherapy to be the single most important predictor of response to therapy in childhood ALL. In spite of the crucial role of GCs in ALL therapy, the mechanisms of cell death induced upon GC exposure are poorly understood. Understanding the pathway(s) involved in GC mediated cell death is a crucial first step in understanding the mechanisms of GC resistance in ALL.

Dr. Gurbuxani also has a broad interest in cell death pathways and mechanisms of resistance to chemotherapy-induced cell death in all hematopoietic tumors. Therapy-related acute myeloid leukemias are notoriously resistant to conventional chemotherapy. Novel therapies currently under development or clinical investigation are designed to target specific biologic pathways that are crucial to leukemogenesis and the survival of therapy-related leukemias. These new compounds are likely to trigger new pathways of cell death and may be limited by novel mechanisms of resistance. Dr. Gurbuxani is working with other members of the University of Chicago team to decipher the biologic significance of the genotype-phenotype correlations generated from testing the susceptibility of leukemic cells to various anti-leukemic agents.

Dr. Gurbuxani is also interested in the process of hematopoiesis, particularly the pro-survival signals required during hematopoietic differentiation. His additional interests include the biology of myeloproliferative neoplasms.

Selected Publications from 2010 – 2011

  • Small S, Keerthivasan G, Huang Z, Gurbuxani S, Crispino JD. Overexpression of survivin initiates hematologic malignancies in vivo. Leukemia 24:1920-1926, 2010.
  • Huang QQ, Perlman H, Huang Z, Birkett R, Kan L, Agrawal H, Misharin A, Gurbuxani S, Crispino JD, Pope RM. FLIP: a novel regulator of macrophage differentiation and granulocyte homeostasis. Blood 116:4968-4977, 2010.

Reviews/Editorials

  • Godley LA, Cunningham J, Dolan ME, Huang RS, Gurbuxani S, McNerney ME, Larson RA, Leong H, Lussier Y, Onel K, Odenike O, Stock W, White KP, Le Beau MM. An integrated genomic approach to the assessment and treatment of acute myeloid leukemia. Semin Oncol 38:215-224, 2011.

Selected Presentations

  • “Molecular Mechanisms of Glucocorticoid Induced Cell Death in Acute Lymphoblastic Leukemia”
    Invited Speaker at the Tumor Biology Seminar, Robert H. Lurie Comprehensive Cancer Center, Northwestern University
    Chicago, IL
    October 2010