Jason Karpac, PhD
Education and Post-Graduate Training
Dr. Jason Karpac received his BS in molecular biology from Grove City College in 2003. He obtained his PhD in neuroscience and neuroendocrinology from the University of Oklahoma Health Sciences Center and the Oklahoma Medical Research Foundation in 2007 working with Dr. Ute Hochgeschwender. He then pursued postdoctoral research in Dr. Heinrich Jasper’s laboratory, first at the University of Rochester and then at the Buck Institute for Research on Aging. Karpac was a research assistant professor at the Buck Institute for Research on Aging from 2013-2014 before joining the faculty at the Texas A&M College of Medicine in September 2014.
Our laboratory is broadly interested in the cellular and systemic (endocrine) adaptive signaling networks that regulate metabolic homeostasis, and subsequently affect the aging process. The ability to endure bouts of starvation and infection is a primitive challenge in multi-cellular organisms. In order to combat these ancient stressors, organisms have developed tightly regulated and highly integrated adaptive signaling mechanisms to promote survival through the maintenance of metabolic homeostasis. It is also imperative that these responses are dynamically controlled, as changes in the regulation of adaptive mechanisms (i.e. chronic inflammation and insulin resistance) can lead to metabolic dysfunction and age-related diseases. The laboratory primarily uses the fruit flyDrosophilaas model to investigate the function of these signaling networks at multiple levels of biological organization: from molecules, to cells and tissues, to tissue-tissue interactions, to whole organism physiology and aging. Some specific areas of research interest currently include:
- understanding how the integration of insulin/IGF signaling and NFkB-mediated innate immune responses in various tissues governs specific aspects of metabolic function and tissue aging
- investigating the tissue-specific signaling networks, regulated by insulin/IGF signaling, that govern lipid metabolism in response to metabolic adaptation (i.e. dietary changes)
- developingin vivogenetic screens aimed at identifying systemic (endocrine) factors that drive tissue-tissue interactions during aging to control metabolic homeostasis and longevity
- Mlih, M., Khericha, M., Birdwell, C., West, AP., Karpac, J. (2018). A virus-acquired host cytokine controls systemic aging by antagonizing apoptosis. PLoS Biology, 16(7): e2005796.
- Fuentes, NR., Mlih, M., Barhoumi, R., Fan, YY., Hardin, P., Steele, TJ., Behmer, S., Prior, IA., Karpac, J., Chapkin, RS. (2018). Long chain n-3 fatty acids attenuate oncogenic KRas-driven proliferation by altering plasma membrane nanoscale proteolipid composition. Cancer Research, DOI: 10.1158/0008-5472.
- Zhao, X., Karpac, J. (2017). Muscle directs diurnal energy homeostasis through a myokine-dependent hormone module in Drosophila. Current Biology, 27(13): 1941-1955.
- Luis Miguel, N., Wang, L., Ortega, M., Deng, H., Katewa, SD., Wai-Lun Li, P., Karpac, J., Jasper, H., Kapahi, P. (2016). Intestinal IRE1 is required for increased triglyceride metabolism and longer lifespan under dietary restriction. Cell Reports, 17(5): 1207-1216.
- Guo, L.*, Karpac, J.*, Tran, S., Jasper, H. (2014). PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell, 156(1-2): 109-122. *equal contribution.http://www.ncbi.nlm.nih.gov/pubmed/24439372
- Wang, L.*, Karpac, J.*, Jasper, H. (2014). Promoting longevity by maintaining metabolic and proliferative homeostasis. J Exp Biol., 217(Pt 1):109-18. *equal contribution.http://www.ncbi.nlm.nih.gov/pubmed/24353210
- Karpac, J.#, Biteau, B., Jasper, H. (2013). Misregulation of an adaptive metabolic response contributes to the age-related disruption of lipid homeostasis in Drosophila. Cell Reports, DOI:10.1016/ j.celrep.2013.08.004. #corresponding author.http://www.ncbi.nlm.nih.gov/pubmed/24035390
- Karpac, J., Jasper, H. (2013). Aging: Seeking mitonuclear balance. Cell, 154(2);271-273.http://www.ncbi.nlm.nih.gov/pubmed/23870118
- Kapuria, S., Karpac, J., Biteau, B., Hwangbo, DS., Jasper, H. (2012). Notch-mediated suppression of TSC2 expression regulates cell differentiation in the Drosophila intestinal stem cell lineage. PLoS Genetics, 8(11): e1003045.http://www.ncbi.nlm.nih.gov/pubmed/23144631
- Karpac, J., Younger, A., Jasper, H. (2011). Dynamic coordination of innate immune signaling and Insulin signaling regulates systemic responses to localized DNA damage. Developmental Cell, 20(6):841-54.http://www.ncbi.nlm.nih.gov/pubmed/21664581
- Karpac, J., Jasper, H. (2011). Metabolic Homeostasis: HDACs Take Center Stage. Cell, 145(4):497-9.http://www.ncbi.nlm.nih.gov/pubmed/21565608
- Biteau, B., Karpac, J., Hwangbo, D., and Jasper, H. (2010). Regulation of Drosophila lifespan by JNK signaling. Exp Gerontol, 46(5):349-54.http://www.ncbi.nlm.nih.gov/pubmed/21111799
- Biteau, B.*, Karpac, J.*, Supoyo, S., DeGennaro, M., Lehmann, R., and Jasper, H. (2010). Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genetics, 6(10): e1001159. *equal contribution. http://www.ncbi.nlm.nih.gov/pubmed/20976250
- Karpac, J., Hull-Thompson, J., Falleur, M., and Jasper, H. (2009). JNK signaling in insulin producing cells is required for adaptive responses to stress in Drosophila. Aging Cell, 8 288-295.http://www.ncbi.nlm.nih.gov/pubmed/19627268
- Karpac, J., and Jasper, H. (2009). Insulin and JNK: optimizing metabolic homeostasis and lifespan. Trends Endocrinol Metab, 20, 100-106.http://www.ncbi.nlm.nih.gov/pubmed/19251431
- Karpac, J., Kern, A., Kim, S., Brush, S., Bui, S., Hunnewell, P. & Hochgeschwender, U. (2008). Failure of adrenal corticosterone production in POMC-deficient mice results from lack of integrated effects of POMC peptides on multiple factors. Am J Physiol Endocrinol Metab, 295(2):E446-55.http://www.ncbi.nlm.nih.gov/pubmed/18559987
- Karpac, J., Kern, A. & Hochgeschwender, U. (2007). Pro-opiomelanocortin peptides and the adrenal gland. Mol Cell Endocrinol, 265-266:29-33.http://www.ncbi.nlm.nih.gov/pubmed/17222502
- Ostwald, D., Karpac, J. & Hochgeschwender, U. (2006). Effects on hippocampus of lifelong absence of glucocorticoids in the pro-opiomelanocortin null mutant mouse reveal complex relationship between glucocorticoids and hippocampal structure and function. J Mol Neurosci, 28, 291-302.http://www.ncbi.nlm.nih.gov/pubmed/16691017
- Karpac, J., Ostwald, D., Bui, S., Hunnewell, P., Shankar, M. & Hochgeschwender, U. (2005). Development, maintenance, and function of the adrenal gland in early post-natal pro- opiomelanocortin-null mutant mice. Endocrinology, 146, 2555-62. http://www.ncbi.nlm.nih.gov/pubmed/15731356