Riyaz M. Basha, Ph.D.

Riyaz M. Basha, PhD Assistant Professor Oncology Senior Research Scientist Principal Investigator Experimental Therapeutics Laboratory Lab Members Umesh Sankpal, PhD        Postdoctoral Scientist Ibrahim Shukoor, PhD       Postdoctoral Scientist Sarah Connelly, BS            Laboratory Technician Chris Lee, MS                      Laboratory Technician

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Biography

Dr. Basha joined MD Anderson Cancer Center - Orlando (MDACCO) Cancer Research Institute in April, 2008. He graduated with Ph.D. from Sri Venkateswara University, Tirupati, India, and received postdoctoral training in Pharmacology and Toxicology in the College of Pharmacy at University of Rhode Island, Kingston, RI. Before joining MDACCO, Dr. Basha worked as a Principal Scientist in Vitrimark (Providence, RI) and extensively worked on the discovery of biomarkers for breast cancer and prostate cancer using nanotechnology. Dr. Basha received the young scientist travel award from the Asian Pacific Society for Neurochemistry (APSN) in 1998 and FOUR awards from the Society of Toxicology (SOT) for his research presentations in 2001-03 and 2006 during the SOT annual meetings. Apart from several invited talks, Dr. Basha delivered FOUR plenary or special invited lectures in special symposia in Toronto, Canada (DOHaD-Developmental Origins of Health and Disease meeting, 2006), San Diego, CA (SOT annual meeting, 2006), Tirupati, India (ISEPEHH-International Symposium on Environmental Pollution Ecology and Human Health, 2009), and Dubai (International Conference on Drug Discovery and Therapy, February 2012). Dr. Basha published more than 40 peer reviewed research articles and serves as a reviewer for a dozen scientific journals and Guest Editor for two Bentham Science Publications journals, Medicinal Chemistry (hot topic issue on "Contemporary Approaches in Cancer Therapy", and Current Medicinal Chemistry (hot topic issue on Molecular tools in Cancer Diagnosis and Therapy).

Research Summary

My laboratory is primarily interested in studying the molecular aspects underlying the anti-cancer activity of non-steroidal anti-inflammatory drugs (NSAIDs) such as tolfenamic acid. The NSAIDs are largely used for the treatment of acute or chronic conditions with pain and inflammation. Evidence from a wide range of sources suggests that chronic administration of NSAIDs reduced the risk of cancer incidences. Both the epidemiological and animal studies showed an inverse association between the incidence of various cancers and the use of aspirin or other NSAIDs. Studies from our laboratory and collaborators provided substantial evidence on the anti-cancer activity of tolfenamic acid for the potential applications in pancreatic, esophageal and lung cancers. In general, the anti-cancer activity of tolfenamic acid is attributed to its inhibitory actions on the expression of specific Specificity Protein (Sp) transcription factors. Sp proteins regulate the expression of key genes associated with tumorigenesis and metastasis.Tolfenamic acid suppresses the expression of Sp1, Sp3 and Sp4 and induces the inhibition of vascular epithetical growth factor (VEGF), c-Met and Akt phosphorylation in human cancer cells. Sp1 and Sp3 regulate the expression of inhibitor of apoptosis protein, survivin that is associated with resistance to chemo and radiation therapy and tolfenamic acid inhibits survivin expression through down-regulating Sp1 and Sp3. Recent studies from our laboratory further confirmed that tolfenamic acid is more effective on other cancers including leukemia, medullobalstoma, neuroblastoma, and ovarian cancer. This will open the door for further research in identifying novel targets associated with the anti-cancer activity of tolfenamic acid.

Other areas of interest include identifying micro-structural biomarkers for prostate cancer using nanotechnology and identifying / developing potent anti-cancer agents from the active ingredients isolated from medicinal plants.

Selected Peer-reviewed Publications

Sankpal, U.T., Maliakal, P., Bose, D., Kayaleh, O. R., Buchholz, D., and Basha, R.  Expression of Specificity Protein Transcription Factors in Pancreatic Cancer and their Association in Diagnosis, Prognosis and Therapeutic Target. Curr. Med. Chem. In press.

Sankpal, U.T., Pius, H., Khan, M., Shukoor, M.I., Maliakal, P., Lee, C.M., Abdelrahim, M., Connelly, S.F., and Basha, R. Environmental Factors in Causing Human Cancers: Emphasis on Tumorigenesis. Tumor Biology. In press.

Sankpal, U.T, Abdelrahim, M., Connelly, S.F., Lee, C.M., Madero-visbal, R., Colon, J., C.H., Smith, J., Safe, S., Malikal, P., and Basha, R. (2012). Small molecule tolfenamic acid inhibits PC-3 cell proliferation and invasion in vitro, and tumor growth in orthotopic mouse model for prostate cancer. The Prostate. [Epub ahead of print]. PMID: 22473873.

Eslin D., Sankpal, U.T., Chris Lee, Sutphin, R., Maliakal, P., Currier, E., Sholler, G., and Basha, R. Tolfenamic acid inhibits cell proliferation and induces cell apoptosis in neuroblastoma cell lines: a novel therapeutic agent for neuroblastoma. Mol. Carcinogenesis. Epub ahead of print. Dec., 2011. PMID: 22213339.

Rahim, A., Nafi-valencia, E., Siddiqi, S., Basha, R., Runyon, C.C., Siddiqi, S.A. (2012). Proteomic Analysis of the Very Low Density Lipoprotein (VLDL) Transport Vesicles.  J Proteomics. 75(7):2225-35. PMID: 22449872.

Maliakal, P., Abdelrahim, M., Sankpal, U.T., Baker, C.H., Herrera, L., Safe, S., Abudayyeh, A, S. Kaja, and Basha, M.R. (2012). Chemopreventive effects of tolfenamic acid against esophageal tumorigenesis in rats. Invest New Drugs. 30(3):853-61. PMID: 21197621.

Basha, R. (2011). Contemporary Approaches in Cancer Therapy. Med Chem. 7(5): 430-431. PMID: 22022993.

Sankpal, U.T., Goodison, S., Abdelrahim, M., and Basha, R. (2011). Targeting SP1 transcription factors in prostate cancer therapy. Med Chem. 7(5): 518-525. PMID: 22022994.

Sankpal, U.T., Kaja, S., Rahim, A., Patel, P., Abdelrahim, M., and Basha, R. (2011). Role of environment in human cancers. In: Environment and Health.  Eds. Reddy, G.R., Flora, S.J.S., Basha, R., Narosa Publishing house, New Delhi. pp 136-147.

Maliakal, P., Sankpal, U.T., Basha, R., Maliakal, C., Ledford A., and Wanwimolruk, S. (2011). Relevance of drug metabolizing enzymes activity modulation by tea polyphenols in the inhibition of esophageal tumorigenesis Med Chem. 7(5): 480-487. PMID: 21801144.

Adwan, L.I., Basha, R., Abdelrahim, M., Zawia, N.H. (2011). Tolfenamic acid interrupts the de novo synthesis of the amyloid precursor protein and lowers amyloid beta via a transcriptional pathway. Curr Alzheimer Res. 8(4): 385-892. PMID: 21557719.

Basha, R., Ingersoll, S.B., Sankpal, U.T, Ahmad, S., Baker, C.H., Edwards, J.R., Holloway, R.W., Kaja, S., and Abdelrahim, M. (2011). Tolfenamic Acid Inhibits Ovarian cancer cells growth and decreases the expression of c-Met and survivin through suppressing the transcription factors Sp1 and Sp3. Gyn Oncology. 122(1): 163-70. PMID: 21496890.

Basha, R., Baker, C.H., Sankpal, U., Ahmad, S., Safe, S., Abdelrahim, M. (2011). Therapeutic Applications of Non-Steroidal Anti-Inflammatory Drugs in Cancer: Special Emphasis on Tolfenamic Acid. Front Biosci (Schol Ed). 3: 797-805. PMID: 21196413.

Colon, J., Basha, M.R., Madero-Visbal, R., Konduri, S., Baker, C.H., Herrera, L.J., Safe, S., Sheikh-Hamad, D., Abudayyeh, A., Alvarado, B., Abdelrahim, M. (2011). Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice. Invest. New Drugs, 29(1):41-51. PMID: 19851711.

Basha, R., Reddy, G.R. (2010). Developmental exposure to lead and late life abnormalities of the nervous system. Indian J Exp Biol. 48: 636-41. PMID: 20929048.

Aziz, N., Jha, A., Thanos, C., Basha, R, Bose, A. (2010). Structural markers in prostate cancer serum imaged ex vivo using cryogenic transmission electron microscopy. J Electron Microsc (Tokyo). 59(5): 451-6. PMID: 20445004.

Jutooru, I, Chadalapaka, G., Abdelrahim, M., Basha, M.R., Samudio, I., Konopleva, M., Andreeff, M, and Safe, S. (2010). Methyl 2-Cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) Decreases Specificity Protein (Sp) Transcription Factors and Inhibits Pancreatic Tumor Growth. Mol Pharmcol. 78(2): 226-36. PMID: 20488920.

Zawia, N.H., Basha, R. (2010).  Developmental lead exposure epigenetics and late onset of Alzheimer’s disease. In: Developmental Neurotoxicology Research, (Eds. Wang, C., Slikker, W.), pp 143-62, John Wiley & Sons Inc., Hoboken, NJ, USA.

Abdelrahim, M., Konduri, S., Basha, M.R., Abudayyeh, A., Baker, C.H. (2010). Angiogenesis: A recent update and potential drug approaches. Int. J. Oncol. 36: 5-18. PMID: 19956828.

Konduri, S., Colon, J., Baker, C.H., Safe S., Abbruzzese, J.L, Abudayyeh, A., Basha, M.R., and Abdelrahim, M. (2009). Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression. Mol. Cancer Ther. 8(3): 533-542. PMID:19258429.

Basha, M.R., Baker, C.H., Abdelrahim, M. (2009). Biomarkers clinical relevance in cancer: Emphasis on breast cancer and prostate cancer. Curr. Trends Biotechnol. Pharmacy 3(1): 1-7.

Dosunmu, R., Wu, J., Adwan, L., Maloney, B., Basha, M.R., McPherson, C.A., Harry, J.G., Rice, D.C., Zawia, N.H., Lahiri, D.K. (2009). Lifespan profiles of AD associated genes and their products in monkeys and mice. J. Alzheimers Dis. 18(1): 211-230. PMID: 19584442.

Wu, J., Basha, M.R., Brock, B., Cox, D.P., Cardozo-Pelaez, F., McPherson, C.A., Harry, J., Rice, D.C., Maloney, B., Chen, D., Lahiri, D.K, Zawia. N.H. (2008). Alzheimer's disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): Evidence for a developmental origin and environmental link for AD. J. Neurosci. 28(1): 3-9. PMID: 18171917.

Brock, B., Basha, R., DiPalma, K., Anderson, A., Harry, G.J., Rice, D.C,, Maloney, B., Lahiri, D.K, Zawia, N.H. (2008). Co-localization and distribution of cerebral APP and SP1 and its relationship to amyloidogenesis. J. Alzheimers Dis. 13(1): 71-80. PMID: 18334759.

Lahiri, D.K., Maloney, B., Basha, M.R., Ge, Y.W., Zawia, N.H. (2007). How and when environmental agents and dietary factors affect the course of Alzheimer’s disease: The “LEARn” model (Latent Early Associated Regulation) may explain the triggering of AD.  Curr. Alzheimer’s Res. 4(2): 219-228. PMID: 17430250.

Dosunmu R, Wu, J., Basha M.R., Zawia, N.H. (2007). Environmental and dietary risk factors in Alzheimer’s disease: An overview. Expert Rev. Neurotherapeutics 7: 887-900. PMID: 17610395.

White, L.D., Cory-Slechta, D.A., Gilbert, M.E., Tiffany-Castiglioni, E., Zawia, N.H., Virgolini, M., Rossi-George, A., Lasley, S.M., Qian, Y., Basha, M.R. (2007). New and evolving concepts in the neurotoxicology of lead. Toxicol. Appl. Pharmacol. 225(1): 1-27. PMID: 17904601.

Wu, J., Basha, M.R., Zawia, N.H. (2007). The environment, epigenetics and amyloidogenesis. J. Mol. Neurosci. 34(1): 1-7. PMID: 18157652.

Bakheet, S.A., Basha, M.R., Zawia, N.H. (2007). Lead exposure: expression and functionality of oct-2 in the developing rat brain. Toxicol. Sci. 95(2): 436-442. PMID: 17093203.

Bolin, C.S., Basha, M.R., Cox, D., Zawia, N.H., Maloney, B., Lahiri, D. K., Cardozo-Pelaez, F. (2006). Exposure to lead (Pb) and the developmental origin of oxidative DNA damage in the aging brain.  FASEB J. 20(6): 788-790. PMID: 16484331.

Basha, M.R., Braddy, N.S., Zawia, N.H., Kodavanti, P.R.S. (2006). Ontogenetic alterations in certain nuclear transcription factors in cerebellum and hippocampus following perinatal exposure to commercial PCB mixture. NeuroToxicology 27: 118-124. PMID: 16159668.

Zawia, N.H., Basha, M.R. (2005). Environmental risk factors and developmental basis for Alzheimer's disease. Rev.  Neurosci. 16: 325-337. PMID: 16519009.

Basha, M.R., Murali, M., Siddiqi, H.K., Ghosal, K., Siddiqi, O.K., Lashuel, H.A., Ge, Y.W., Lahiri, D.K., Zawia, N.H. (2005). Exposure to lead (Pb) promotes ß-Amyloid aggregation but does not affect the proteolytic processing of amyloid precursor protein. FASEB J. 19(14): 2083-2084. PMID: 16230335.

Basha, M.R., Wei, W., Bakheet, S.A., Benitez, N., Siddiqi, H.K., Ge, Y., Lahiri, D.K., Zawia, N.H. (2005). The fetal-basis of amyloidogenesis: Exposure to lead and latent over expression of amyloid precursor protein and ß-amyloid in the aging brain. J.  Neuroscience, 25(4): 823-829. PMID: 15673661.

Basha, M.R., Wei, W., Reddy, G.R., Zawia, N.H. (2004). Zinc finger transcription factors mediate perturbations of brain gene expression elicited by heavy metals. In: Molecular Neurotoxicology Environmental Agents and Transcription-Transduction Coupling, (Ed. N. H. Zawia), pp. 43-64, CRC Press, USA

Zawia, N.H., Basha, M.R., Razmiafshari, M. (2003). An electrophoretic method to determine the ability of xenobiotic metals to bind a specific protein domain. Curr. Protocols Toxicol. 12(11): 1-8.

Basha, M.R., Wei, W., Brydie, M, Razmiafshari, M., Zawia, N.H. (2003). Lead induced developmental perturbations in hippocampal Sp1 DNA-binding are prevented by Zinc. In vivo evidence for Pb and Zinc competition.  Int. J. Dev. Neurosci. 21(1): 1-12. PMID: 12565691.

Atkins, D.S., Basha, M.R., Zawia, N.H. (2003). Intracellular signaling pathways involved in mediating the effects of lead on the transcription factor Sp1. Int. J. Dev. Neurosci. 21: 235-244. PMID: 12850056.

Reddy, G.R., Basha, M.R., Bhuvaneswari, C., Suresh, A., Baker, J.L., Shafeek, S.A., Heinz, J., Chetty, C.S. (2003). Lead-induced effects on acetyl cholinesterase activity in cerebellum and hippocampus of developing rat. Int. J. Dev. Neurosci. 21(6): 347-352. PMID: 12927583.

Basha, M.R., Wei, W., Zawia, N.H. (2003). PCBs and environmental metal Pb exacerbate Ab aggregation and its cytotoxicity in PC12 cells. Ogranohalogen Compounds 65: 12-15.

Basha, M.R., Brady, N.S., Kodavanti, P.S., Zawia, N.H. (2002). Changes in the DNA-binding of several transcription factors in the developing rat cerebellum by PCBs. Ogranohalogen Compounds 57: 381-383.