Imagine sitting at the doctors, waiting to find out why you are not feeling well. Test after test, there often is not an answer. A few years back, Jeremy went through this exact struggle, waking up in the morning with incredible sore wrists, fingers, and other joints. As it got worse, the doctors thought one thing after another. Finally, after multiple visits, they realized it was psoriatic arthritis.
Getting into Precision Medicine seems easy, but tools for clinicians to use have been slow in development. When Jeremy joined the lab of Howard Jacob, whose lab was featured in One in a Billion: The Story of Nic Volker and the Dawn of Genomic Medicine, he realized how unfair the healthcare system is based on luck. Families with kids having rare disorders often spend millions of dollars trying to find out the cause of disease.
Jeremy began moving into using the DNA and RNA from individuals to understand disease risks and develop better tools to diagnose, understand, and potentially treat disease. Most labs take on studying only a single disease, leaving many diseases poorly studied and not fully appreciating how diseases are similar and different. The Prokop lab strives to understand any disease and why they happen, with the hopes of one day predicting adverse outcomes before they ever manifest.
Areas of Expertise (3)
Pediatrics and Human Development
Genes and Genetic Variants
Physiological Genomics New Investigator Award
American Physiological Society (APS)
University of Akron: PhD, Integrated Bioscience 2013
University of Akron: BS, Animal Physiology and Microbiology 2008
Journal Articles (5)
C Joy Shepard, Sara G Cline, David Hinds, Seyedehameneh Jahanbakhsh, and Jeremy W Prokop
2019 Genetics of multiple sclerosis (MS) are highly polygenic with few insights into mechanistic associations with pathology. In this paper, we assessed MS genetics through linkage disequilibrium and missense variant interpretation to yield a MS gene network. This network of 96 genes was taken through pathway analysis, tissue expression profiles, single cell expression segregation, expression quantitative trait loci (eQTLs), genome annotations, transcription factor (TF) binding profiles, structural genome looping, and overlap with additional associated genetic traits. This work revealed immune system dysfunction, nerve cell myelination, energetic control, transcriptional regulation, and variants that overlap multiple autoimmune disorders. Tissue-specific expression and eQTLs of MS genes implicate multiple immune cell types including macrophages, neutrophils, and T-cells, while the genes in neural cell types enrich for oligodendrocyte and myelin sheath biology. There are eQTLs in linkage with lead MS variants in 25 genes including the multi-tissue eQTL, rs9271640, for HLA-DRB1/DRB5. Using multiple functional genomic databases, noncoding variants were identified that disrupt TF binding for GABPA, CTCF, EGR1, YY1, SPI1, CLOCK, ARNTL, BACH1, and GFI1. Overall, this manuscript suggests multiple genetic mechanisms for MS associated variants while highlighting the importance of a systems biology and network approach when elucidating intersections of the immune and nervous system.
Sahar Nissim, Ignaty Leshchiner, Joseph D. Mancias, Matthew B. Greenblatt, Ophélia Maertens, Christopher A. Cassa, Jill A. Rosenfeld, Andrew G. Cox, John Hedgepeth, Julia I. Wucherpfennig, Andrew J. Kim, Jake E. Henderson, Patrick Gonyo, Anthony Brandt, Ellen Lorimer, Bethany Unger, Jeremy W. Prokop, Jerry R. Heidel, Xiao-Xu Wang, Chinedu I. Ukaegbu, Benjamin C. Jennings, Joao A. Paulo, Sebastian Gableske, Carol A. Fierke, Gad Getz, Shamil R. Sunyaev, J. Wade Harper, Karen Cichowski, Alec C. Kimmelman, Yariv Houvras, Sapna Syngal, Carol Williams & Wolfram Goessling
2019 Pancreatic ductal adenocarcinoma is an aggressive cancer with limited treatment options1. Approximately 10% of cases exhibit familial predisposition, but causative genes are not known in most families2. We perform whole-genome sequence analysis in a family with multiple cases of pancreatic ductal adenocarcinoma and identify a germline truncating mutation in the member of the RAS oncogene family-like 3 (RABL3) gene. Heterozygous rabl3 mutant zebrafish show increased susceptibility to cancer formation. Transcriptomic and mass spectrometry approaches implicate RABL3 in RAS pathway regulation and identify an interaction with RAP1GDS1 (SmgGDS), a chaperone regulating prenylation of RAS GTPases3. Indeed, the truncated mutant RABL3 protein accelerates KRAS prenylation and requires RAS proteins to promote cell proliferation. Finally, evidence in patient cohorts with developmental disorders implicates germline RABL3 mutations in RASopathy syndromes. Our studies identify RABL3 mutations as a target for genetic testing in cancer families and uncover a mechanism for dysregulated RAS activity in development and cancer.
Cody Plasterer, Shirng-Wern Tsaih, Amy R. Peck, Inna Chervoneva, Caitlin O’Meara, Yunguang Sun, Angela Lemke, Dana Murphy, Jennifer Smith, Sophia Ran, Albert J. Kovatich, Jeffrey A. Hooke, Craig D. Shriver, Hai Hu, Edith P. Mitchell, Carmen Bergom, Amit Joshi, Paul Auer, Jeremy Prokop, Hallgeir Rui, Michael J. Flister
2019 Understanding the molecular mediators of breast cancer survival is critical for accurate disease prognosis and improving therapies. Here, we identified Neuronatin (NNAT) as a novel antiproliferative modifier of estrogen receptor-alpha (ER+) breast cancer.
JW Prokop, RJ Duff, HC Ball, DL Copeland, RL Londraville
2012 Leptin is a circulating protein which regulates dietary intake through binding the leptin receptor. Numerous labs have used known structures and mutagenesis to study this binding process in common animal models (human, mouse and rat). Understanding this binding process in other vertebrate species will allow for a better understanding of leptin and leptin receptor function. The binding site between leptin and leptin receptor is highly conserved in mammals as confirmed through sequence alignments mapped onto structures of both leptin and leptin receptor. More variation in this interaction is found in lizard and frog sequences. Using our models, we show that the avian leptin sequences have far less variation in the binding site than does the leptin receptor. This analysis further suggests that avian leptins are artifactual. In fish, gene duplication events have led to the expression of multiple leptin proteins. These multiple leptin proteins have variation in the regions interacting with leptin receptor. In zebrafish and the Japanese rice fish, we propose that leptin A has a higher binding energy than does B. Differing binding energies are evidence of either divergent functions, different binding confirmations, or other protein partners of leptin B.
Donald L Copeland, Robert Joel Duff, Qin Liu, Jeremy Prokop, Richard Lyle Londraville
2011 All organisms face tradeoffs with regards to how limited energy resources should be invested. When is it most favorable to grow, to reproduce, how much lipid should be allocated to storage in preparation for a period of limited resources (e.g. winter), instead of being used for growth or maturation? These are a few of the high consequence fitness ‘decisions’ that represent the balance between energy acquisition and allocation. Indeed, for animals to make favorable decisions about when to grow, eat, or reproduce, they must integrate signals among the systems responsible for energy acquisition, storage, and demand. We make the argument that leptin signaling is a likely candidate for an integrating system. Great progress has been made understanding the leptin system in mammals, however our understanding in fishes has been hampered by difficulty in cloning fish orthologues of mammalian proteins and (we assert), underutilization of the comparative approach.