Krishna Prasadan, PhD
- Director, Cell Imaging Core Laboratory and Research Assistant Professor of Surgery
Administrative Assistant: Tamara Daviston
For the past twenty-one years, Prasadan's research involved finding a cure for diabetes. He has published extensively in this area as the first author, as well as in collaboration with hiscolleagues. His research work identified a role for glucagon and alpha cell-derived peptides in pancreatic endocrine differentiation during development. Further discoveries from their lab and by others have shown that glucagon may have a role in regulating beta-cell function in an adult islet. Their most recent finding now suggests that glucagon or alpha cell-derived signals may even provide a protective niche for beta cells.
One of his current interests is identifying those alpha cells that originated paracrine signals that control beta-cell function, and discovering such signaling events could significantly transform and advance treatment strategies for diabetes. They have shown that the intraductal infusion of AAV serotype 8 contained transcription factors Pdx1 and MafA, as well as a GFP reporter under the CMV promoter (AAV8-CMV-PM-GFP) rescued diabetic phenotype in mice within seven days. Now they have made similar significant progress in regards to our gene therapy in Non-human primates (NHPs). In diabetic NHPs, following gene therapy, they have been able to decrease exogenous insulin requirements by more than 50% and saw improved levels of serum C-peptide. Prior to seeking FDA approval for translation to humans, they are conducting a larger study on NHP's for final optimizations on viral construct, titer, and promoter.
Prasadan has also been involved in the role of TGF beta signaling in pancreas development and function for several years. Recently they discovered that TGF-beta signaling molecule smad2 has led to an improvement in beta-cell function. They are now attempting to develop a therapeutic strategy for the treatment of diabetes, targeting smad2 signaling in beta cells.
In addition to his research, over the past 21 years, Prasadan had other academic responsibilities. He has co-mentored and trained more than 20 clinical research fellows, each fellow for at least two years. Since 2014, he has taken charge as the director of imaging core at UPMC Children's hospital of Pittsburgh. The facility has several confocal microscopes, laser capture microscopes, and other live-cell imaging systems. He has provided consultations and training to several hundred researchers on various imaging techniques for their research.
Professional and Scientific Society Memberships:
- American Diabetes Association, 2000-2006
- American Association of Advancement of Science, 2001-2006
- American Society of Cell Biology, 2003-2006
Education & Training
- BS, Zoology, University of Calicut (India), 1980
- MS, Life Sciences, Sardar Patel University (India), 1983
- PhD, Zoology, Sardar Patel University (India), 1987
Chen, C., Shiota, C., Agostinelli, G., Ridley, D., Jiang, Y., Ma, J., Prasadan, K., Xiao, X., and Gittes, G. K. (2019) Evidence of a developmental origin for beta-cell heterogeneity using a dual lineage-tracing technology. Development146
Xiao, X., Guo, P., Shiota, C., Zhang, T., Coudriet, G. M., Fischbach, S., Prasadan, K., Fusco, J., Ramachandran, S., Witkowski, P., Piganelli, J. D., and Gittes, G. K. (2018) Endogenous Reprogramming of Alpha Cells into Beta Cells, Induced by Viral Gene Therapy, Reverses Autoimmune Diabetes. Cell Stem Cell22, 78-90 e74
Xiao, X., Fischbach, S., Zhang, T., Chen, C., Sheng, Q., Zimmerman, R., Patnaik, S., Fusco, J., Ming, Y., Guo, P., Shiota, C., Prasadan, K., Gangopadhyay, N., Husain, S. Z., Dong, H., and Gittes, G. K. (2017) SMAD3/Stat3 Signaling Mediates beta-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis-Related Diabetes. Diabetes66, 2646-2658
Xiao, X., Chen, C., Guo, P., Zhang, T., Fischbach, S., Fusco, J., Shiota, C., Prasadan, K., Dong, H., and Gittes, G. K. (2017) Forkhead Box Protein 1 (FoxO1) Inhibits Accelerated beta Cell Aging in Pancreas-specific SMAD7 Mutant Mice. J Biol Chem292, 3456-3465
Socorro, M., Criscimanna, A., Riva, P., Tandon, M., Prasadan, K., Guo, P., Humar, A., Husain, S. Z., Leach, S. D., Gittes, G. K., and Esni, F. (2017) Identification of Newly Committed Pancreatic Cells in the Adult Mouse Pancreas. Sci Rep7, 17539
Shiota, C., Prasadan, K., Guo, P., Fusco, J., Xiao, X., and Gittes, G. K. (2017) Gcg (CreERT2) knockin mice as a tool for genetic manipulation in pancreatic alpha cells. Diabetologia60, 2399-2408
Sheng, Q., Xiao, X., Prasadan, K., Chen, C., Ming, Y., Fusco, J., Gangopadhyay, N. N., Ricks, D., and Gittes, G. K. (2017) Autophagy protects pancreatic beta cell mass and function in the setting of a high-fat and high-glucose diet. Sci Rep7, 16348
Orabi, A. I., Wen, L., Javed, T. A., Le, T., Guo, P., Sanker, S., Ricks, D., Boggs, K., Eisses, J. F., Castro, C., Xiao, X., Prasadan, K., Esni, F., Gittes, G. K., and Husain, S. Z. (2017) Targeted inhibition of pancreatic acinar cell calcineurin is a novel strategy to prevent post-ERCP pancreatitis. Cell Mol Gastroenterol Hepatol3, 119-128
Fusco, J., Xiao, X., Prasadan, K., Sheng, Q., Chen, C., Ming, Y. C., and Gittes, G. (2017) GLP-1/Exendin-4 induces beta-cell proliferation via the epidermal growth factor receptor. Sci Rep7, 9100
Xiao, X., Fischbach, S., Song, Z., Gaffar, I., Zimmerman, R., Wiersch, J., Prasadan, K., Shiota, C., Guo, P., Ramachandran, S., Witkowski, P., and Gittes, G. K. (2016) Transient Suppression of TGFbeta Receptor Signaling Facilitates Human Islet Transplantation. Endocrinology157, 1348-1356