Molecular Oncology and Biomarkers Program
Harold Harrison, MD Distinguished University Professor
Professor, Biochemistry and Molecular Biology
Professor, Graduate Studies
Professor, Medicine, Hematology and Oncology
Georgia Cancer Center
1410 Laney Walker Blvd., Office: CN-3130
Office Phone: 706-723-0033
Lab Phone: 706-446-4976
My research group is engaged in basic and pre-clinical research on broad areas of cancer prevention, progression, and overcoming chemotherapy resistance. The cancer type and models used in my research are breast, bladder, and prostate cancers. We are interested in the cellular pathways that govern metastatic and therapy-resistant phenotypes and in the isolation and characterization of plant-derived natural products and other compounds that specifically target tumor cells. My laboratory employs tumor models such as tumor-derived continuous cell lines, primary tumor tissues, and patient-derived xenograft and transgenic mouse models.
My research group investigates how cancer cells subvert normal biological processes for their growth, invasion and metastasis to other organs, and how they develop resistance to therapies. Current research work in my laboratory is to understand how muscle-invasive bladder cancers arise, how to predict tumor recurrence, and how cancer stem cell-like tumor cells resist chemotherapy. Furthermore, we are interested in identifying dietary and plant-derived bioactive products to prevent the initiation and progression of prostate and breast cancers. Our work involves a variety of scientific approaches including genome-wide expression analyses, CRISPR/Cas9 technology for generation of tumor cell lines with distinct phenotypes, transgenic and patient-derived xenografts, gene knockout models, and purification of bioactive compounds. My research group has identified molecular markers that potentially determine the response of bladder cancer to chemotherapy, especially the Gemcitabine + Cisplatin chemotherapy combination. The markers: β-Arrestin 1 (ARRB1) and β-Arrestin 2 (ARRB2) are members of the intracellular signaling complex triggered by chemokine receptors. We are currently utilizing the CRISPR/Cas9 technology to investigate the role of β-Arrestins in regulation of differentiation and the cancer stem cell phenotype, metastatic potential and resistance of bladder cancer cells towards chemotherapy.
Hoy JJ, Kallifatidis G, Smith DK, Lokeshwar BL. Inhibition of androgen receptor promotes CXC-chemokine receptor 7-mediated prostate cancer cell survival. Sci Rep. (Nature Publishers) 2017 Jun 8;7(1):3058.
Shamaladevi N, Araki S, Lyn DA, Ayyathurai R, Gao J, Lokeshwar VB, Navarrete H, Lokeshwar BL. The andean anticancer herbal product BIRM causes destabilization of androgen receptor and induces caspase-8 mediated-apoptosis in prostate cancer. Oncotarget. 2016 Dec 20;7(51):84201-84213.
Kallifatidis G, Munoz D, Singh RK, Salazar N, Hoy JJ, Lokeshwar BL. β-Arrestin-2 Counters CXCR7-Mediated EGFR Transactivation and Proliferation. Mol. Cancer Res. 2016 May;14(5):493-503.
Kallifatidis G, Hoy JJ, Lokeshwar BL. Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer. Semin. Cancer Biol. 2016 Oct;40-41:160-169.
Zhang L, Shamaladevi N, Jayaprakasha GK, Patil BS, Lokeshwar BL*. Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice. Oncotarget. 2015 Jun 30 6(18):16379-95.
Salazar N, Muñoz D, Kallifatidis G, Singh RK, Jorda M, Lokeshwar BL*. The Chemokine Receptor CXCR7 interacts with EGFR to Promote Breast Cancer Cell Proliferation. Molecular Cancer.2014, 13:198.
AWARDS AND FUNDING
Dr. J. Harold Harrison Distinguished University Professor in basic sciences.
01/01/2011-12/31/17 (no-cost extension)
Principal Investigator: Lokeshwar, B.L.
Prostate cancer chemoprevention by Allspice derived compound, Ericifolin.
Principal Investigator: Vinata B. Lokeshwar, Role: Co-Investigator.
Dietary combination for prevention of metastatic renal cell carcinoma.
Principal Investigator: Guangyu Wu, Role: Co-investigator.
ARF-1 signaling in prostate cancer.
Funds from Augusta University:
Dr. Harold Harrison Endowed Chair Research Support