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Douglas R. Cavener

Douglas R. Cavener

Main Content

Professor and Verne M. Willaman Dean, Eberly College of Science

110 Huck Life Sciences
University Park, PA 16802
Phone: (814)865-9591
Lab Address: 113 Life Sciences
Lab Phone: (814) 865-1769
Email:

Education

  1. Ph.D., University of Georgia, 1980
  2. M.S., Brown University, 1977
  3. B.A., Pasadena College, 1973

Postdoc Training

  1. Cornell University, 1980-1982

Honors and Awards

  1. Theodosius Dobzhansky Prize, International Society for the Study of Evolution
  2. Fellow of the American Association for the Advancement of Science

Research Interests

Regulatory networks and gene therapy

My research interests encompass genetic regulatory pathways that dynamically control developmental and physiological processes to adapt to internal or external perturbations. Currently, my research group is focused on regulation of metabolic processes that are particularly prone to maladaptations that lead to diseases such as diabetes and metabolic syndrome. In particular we are studying the regulatory role of PERK eIF2 alpha kinase. We have discovered that PERK is a dynamic sensor of physiological/developmental changes and acts to modulate genetic networks for the purpose of adaptation and to acutely regulate intracellular calcium dynamics. The importance of PERK was underscored by our finding that PERK knockout mice display permanent neonatal diabetes, exocrine pancreas atrophy, multiple skeletal dysplasias, severe metabolic dysfunctions, and growth retardation, which perfectly parallels the human Wolcott-Rallison syndrome, also caused by Perk deficiency. Current research is focused on PERK regulation of insulin synthesis and secretion in the pancreatic beta cells and developing gene therapy strategies to correct PERK mutations in humans utilizing CRISPR-Cas9 gene editing.

Evolution and conservation of giraffe and elephant

We are investigating the evolutionary genetic changes underlying the unique morphology and physiology of the giraffe. We have sequenced the giraffe genome as well as a closely related species okapi, which lacks giraffe unique morphology and turbocharged cardiovascular system. By using comparative genome analysis we have identified candidate genes that we propose underlies giraffe long neck and legs and associated cardiovascular adaptations. Current studies are focused on testing the function of these genetic changes as related to giraffe's unique adaptations. Giraffe and African elephants have experienced massive declines in Africa due to poaching, and in support of their conservation we are investigating the population and ecological genetics of the Masai giraffe and the African savannah elephant in Tanzania.

Selected Publications

  1. Ishengoma E, Agaba M, Cavener DR. Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi. PeerJ. 2017 Apr 6;5:e3145. doi: 10.7717/peerj.3145. eCollection 2017. PubMed PMID: 28396824; PubMed Central PMCID: PMC5385128.
  2. Zhu S, McGrath BC, Bai Y, Tang X, Cavener DR. PERK regulates G(q) protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons. Mol Brain. 2016 Oct 1;9(1):87. PubMed PMID: 27716400; PubMed Central PMCID: PMC5045583.
  3. Zhu S, Henninger K, McGrath BC, Cavener DR. PERK Regulates Working Memory and Protein Synthesis-Dependent Memory Flexibility. PLoS One. 2016 Sep 14;11(9):e0162766. doi: 10.1371/journal.pone.0162766. eCollection 2016. PubMed PMID: 27627766; PubMed Central PMCID: PMC5023101.
  4. Agaba M, Ishengoma E, Miller WC, McGrath BC, Hudson CN, Bedoya Reina OC, Ratan A, Burhans R, Chikhi R, Medvedev P, Praul CA, Wu-Cavener L, Wood B, Robertson H, Penfold L, Cavener DR. Giraffe genome sequence reveals clues to its unique morphology and physiology. Nat Commun. 2016 May 17;7:11519. doi: 10.1038/ncomms11519. PubMed PMID: 27187213; PubMed Central PMCID: PMC4873664.
  5. Wang R, McGrath BC, Kopp RF, Roe MW, Tang X, Chen G, Cavener DR. Insulin secretion and Ca2+ dynamics in β-cells are regulated by PERK (EIF2AK3) in concert with calcineurin. J Biol Chem. 2013 Nov 22;288(47):33824-36. doi: 10.1074/jbc.M113.503664. Epub 2013 Oct 10. PubMed PMID: 24114838; PubMed Central PMCID: PMC3837125.
  6. Trinh MA, Kaphzan H, Wek RC, Pierre P, Cavener DR, Klann E. Brain-specific disruption of the eIF2α kinase PERK decreases ATF4 expression and impairs behavioral flexibility. Cell Rep. 2012 Jun 28;1(6):676-88. doi: 10.1016/j.celrep.2012.04.010. Epub 2012 May 24. PubMed PMID: 22813743; PubMed Central PMCID: PMC3401382.
  7. Cavener DR, Gupta S, McGrath BC. PERK in beta cell biology and insulin biogenesis. Trends Endocrinol Metab. 2010 Dec;21(12):714-21. doi: 10.1016/j.tem.2010.08.005. Epub 2010 Sep 17. Review. PubMed PMID: 20850340; PubMed Central PMCID: PMC2991375.
  8. Gupta S, McGrath B, Cavener DR. PERK (EIF2AK3) regulates proinsulin trafficking and quality control in the secretory pathway. Diabetes. 2010 Aug;59(8):1937-47. doi: 10.2337/db09-1064. Epub 2010 Jun 8. PubMed PMID: 20530744; PubMed Central PMCID: PMC2911049.
  9. Wei J, Sheng X, Feng D, McGrath B, Cavener DR. PERK is essential for neonatal skeletal development to regulate osteoblast proliferation and differentiation. J Cell Physiol. 2008 Dec;217(3):693-707. doi: 10.1002/jcp.21543. PubMed PMID: 18683826.
  10. Zhang W, Feng D, Li Y, Iida K, McGrath B, Cavener DR. PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis. Cell Metab. 2006 Dec;4(6):491-7. PubMed PMID: 17141632.
  11. Zhang P, McGrath B, Li S, Frank A, Zambito F, Reinert J, Gannon M, Ma K, McNaughton K, Cavener DR. The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Mol Cell Biol. 2002 Jun;22(11):3864-74. PubMed PMID: 11997520; PubMed Central PMCID: PMC133833.