Janaiah Kota, Ph.D.
Assistant Professor of Medical & Molecular Genetics
Member of the IU Simon Cancer Center & IUPUI Pancreatic Cancer Signature Center
IUSCC-Experimental and Development Therapeutics
Indiana University School of Medicine
- B.S. 1998- Acharya N.G. Ranga Agricultural University (ANGRAU), India
- M.S. 2000- Indian Agricultural Research Institute (IARI), India
- Ph.D. 2005- Indian Agricultural Research Institute (IARI), India
- Post-Doctoral Scientist, 2006-2011- Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital and Johns Hopkins University School of Medicine
- Research Scientist, 2011-2012- Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital.
Our laboratory is focused on understanding the patho-physiological roles of microRNAs (miRNAs) in human diseases with major emphasis on cancer and developing novel miRNA-based therapeutics. miRNAs are small ~18-24 nucleotide non-coding RNAs that regulate gene expression by targeting mRNAs for translational repression, degradation, or both. Although these small RNAs were first discovered for their role in C. elegans development, it is now appreciated that miRNAs regulate a diverse array of cellular processes in eukaryotes. A role for miRNAs in cancer biology has been extensively documented, including cancer cell proliferation, differentiation, survival, migration, and cell death. Virtually all examined cancer types are characterized by abnormal miRNA expression patterns and specific miRNAs are known to act as oncogenes and tumor suppressors. Even though specific miRNAs are often over-expressed, many miRNAs are down regulated in tumors.
Previous studies from my work and others have provided evidence for miRNA replacement as an efficacious and non-toxic anti-cancer therapeutic strategy. In proof-of principle studies, we have demonstrated that systemic delivery of miR-26a, a miRNA whose expression is frequently lost in hepatocellular carcinoma (HCC), using an Adeno Associated Virus (AAV) vector potently suppressed tumor progression in a mouse model of HCC by inhibiting tumor cell proliferation and inducing tumor specific apoptosis. Importantly, off-target effects were not observed. These findings provide evidence that miRNA delivery holds promise as a powerful and highly specific therapeutic modality for treating cancer. Currently, we are engaged in translating these pre-clinical studies into the clinic and extending viral vector mediated miRNA delivery approaches to other cancers, such as pancreatic cancer.
In addition, there are other ongoing research projects that are focused on studying the biological role of miRNAs in oncogenic signaling pathways/disease mechanisms. The ultimate goal of the Kota laboratory is to develop better treatment strategies for various human cancers and improve the survival of patients.
Awards and Honors
Excellence in Research Award, American Society of Gene and Cell Therapy (ASGCT), 2009
Outstanding Post-Doctoral Scientist: Basic Research, The Research Institute at Nationwide Children’s Hospital, 2010
Rosales XQ, Malik V, Sneh A, Chen L, Lewis S, Kota J, Gastier-Foster JM, Astbury C, Pyatt R, Reshmi S, Rodino-Klapac LR, Clark KR, Mendell JR, Sahenk Z. (2013). Impaired regeneration in LGMD2A supported by increased PAX7-positive satellite cell content and muscle-specific microrna dysregulation. Muscle & nerve 47(5):731-739. PMCID3634894
Mendell JR, Rodino-Klapac L, Sahenk Z, Roush K, Bird L, Lowes LP, Alfano L Gomez, AM, Lewis S, Kota J, Malik V, Shontz K, Flanigan KM, Kean JR, Allen HD, Shilling C, Sazani P, Kaye EM (2013). Effect of Eteplirsen on Dystrophin and Walking in Duchenne's muscular dystrophy. Ann Neurol 2013; 74(5): 637-647. PMID23907995
Hsu SS*, Wang B*, Kota J*, Kutay H* , Costinean S*, Bai S*, Yu L, Perle LK, Chivukula RR, Clark KR, Mendell JR, Samson JT , Mendell JT and Ghoshal K. (2012). Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. Journal of Clinical Investigation 122(8):2871–2883. *co-first author. PMCID3408748
Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Clark KR, Mendell JR, Mendell JT. (2009). Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005-1017* PMCID2722880
*Nature Medicine recognized this article as-Notable Advances/Key papers published in 2009
Kota J, Handy CR, Haidet A, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therlfall W, Walker CM, Weisrode SE, Janssen PML, Clark KR, Sahenk Z, Mendell JR, Kaspar BK. (2009). Follistatin gene delivery enhances muscle growth and strength nonhuman primates. Science Translational Medicine 1(6): 6ra15 PMCID2852878
Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Taylor LE, Flanigan KM, Gastier-Foster JM, Astbury C, Kota J, Sahenk Z, Walker CM, Clark KR. (2010). Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Annals of Neurology 2010; 68: 629-38 PMCID2970162
Malik V, Rodino-Klapac LR, Viollet L, Wall C, King W, Al-Dahhak R, Lewis S, Shilling CJ, Kota J, Serrano-Munuera C, Hayes J, Mahan JD, Campbell KJ, Banwell B, Dasouki M, Watts V, Sivakumar K, Bien-Willner R, Flanigan KM, Sahenk Z, Barohn RJ, Walker CM, Mendell JR. (2010). Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Annals of Neurology 67:771-80 PMID 20517938
Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, Sahenk Z, Clark KR. (2009).Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Annals of Neurology 66:290-297 PMID19798725
Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. (2009). Muscle Nerve 39 (3):283-96. PMCID2717722
Panguluri SK, Kota J, Govil JN, Kumar PA, Sharma PC. (2006). AFLP fingerprinting in pigeon pea (Cajanus cajan (L.) Millsp.) and its wild relatives. Genetic Resources and Crop Evolution 53, 523-531
Kota J, Kant K, Dadlani M. (2006). Efficacy of dormancy breaking methods in indica rice varieties. Seed Research 34 (1), 45-49
Kota J, Kant K, Sharma SP (2003). Use of phenol colour test for characterization of rice (Oryza sativa L.) cultivars. Seed Research 31(2),141-147