Douglas J. Epstein
Professor of Genetics
Department: Genetics
Graduate Group Affiliations
Contact information
463 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104
415 Curie Boulevard
Philadelphia, PA 19104
Office: 215 573-4810
Fax: 215 573-5892
Fax: 215 573-5892
Publications
Education:
B.Sc.
McGill University, 1986.
MSc.
McGill University, 1989.
Ph.D.
McGill University, 1993.
Permanent linkB.Sc.
McGill University, 1986.
MSc.
McGill University, 1989.
Ph.D.
McGill University, 1993.
Description of Research Expertise
Research InterestsResearch in my lab focuses on two major themes: gene regulation during brain development and the genetic basis of inner ear morphogenesis. Both areas of investigation use mouse models to study mechanisms of human congenital disorders including brain malformations and hearing loss.
Key words: gene regulation, enhancers, Shh, brain development, hearing loss, cochlea, genetics, genomics, gene therapy
Description of Research
How is Sonic hedgehog expression regulated during brain development?
The Sonic hedgehog (Shh) gene is regulated by a well-characterized set of brain enhancers with essential roles in neurodevelopment. We use Shh enhancer knockout mouse models to:
•Study the mechanisms of enhancer redundancy and 3D folding dynamics of the locus in the developing brain
•Elucidate thalamic development and function
•Decipher neural circuits underlying abnormal motor and sensory information processing that occur in neurodevelopmental disorders
What is the genetic basis of congenital and adult-onset hearing loss?
Hearing loss is the most prevalent sensory deficit in humans. Approximately half of all cases of early onset hearing loss in developed countries have a genetic etiology, with single gene mutations in over 100 different loci identified so far. Despite this progress, the cause of inherited sensorineural hearing loss (SNHL) still remains uncertain in many cases. Remarkably, SNHL is even more common in adults, yet we know much less about the genetic architecture of hearing loss in the adult population. We interrogate the genetic basis of hearing loss:
•By leveraging whole exomes linked to electronic health records in the Penn Medicine Biobank
•As a multidisciplinary team with the Penn Center for Adult Onset Hearing Loss
•By generating mouse models of congenital and adult onset hearing loss, characterizing inner ear phenotypes, and designing novel treatment options
Rotation Projects
Several rotation projects related to the stated goals of the lab are currently available. Contact Dr. Epstein for more information.
Lab personnel:
Jailynn Harke (Graduate Student) co-mentored with Eric Joyce
Staci Rakowiecki (Research Specialist)
Tingfang Chen, Ph.D. (Postdoctoral Fellow)
Sixing Chen, M.Sc. (visiting scholar)
Paraskevi Sgourdou, Ph.D. (Postdoctoral Fellow)
Jeewon (Becca) Lee (Penn Vagelos Scholar)
Selected Publications
Sgourdou P, Schaffler M, Choi K, McCall NM, Burdge J, Williams J, Corder G, Fuccillo MV, Abdus-Saboor I, Epstein DJ.: Impaired pain in mice lacking first-order posterior medial thalamic neurons. Pain 166: 130-143, Jan 2025.Harke J, Lee JR, Nguyen SC, Arab A, Rakowiecki SM, Hugelier S, Paliou C, Rauseo A, Yunker R, Xu K, Yao Y, Lakadamyali M, Andrey G, Epstein DJ, Joyce EF.: Multiple allelic configurations govern long-range Shh enhancer-promoter communication in the embryonic forebrain. Mol Cell 84: 4698-4710, Dec 2024.
Hui D, Mehrabi S, Quimby AE, Chen T, Chen S, Park J, Li B; Regeneron Genetics Center; Penn Medicine Biobank; Ruckenstein MJ, Rader DJ, Ritchie MD, Brant JA, Epstein DJ, Mathieson I.: Gene burden analysis identifies genes associated with increased risk and severity of adult-onset hearing loss in a diverse hospital-based cohort. PLoS Genet 19: e1010584, Jan 2023.
Govek KW, Chen S, Sgourdou P, Yao Y, Woodhouse S, Chen T, Fuccillo MV, Epstein DJ, Camara PG.: Developmental trajectories of thalamic progenitors revealed by single-cell transcriptome profiling and Shh perturbation. Cell Rep 41: 111768, Dec 2022.
Ahmadmehrabi S, Li B, Hui D, Park J, Ritchie M, Rader DJ, Ruckenstein MJ, Epstein DJ, Brant J.: A Genome-First Approach to Rare Variants in Dominant Postlingual Hearing Loss Genes in a Large Adult Population. Otolaryngol Head Neck Surg 166(4): 746-752, Apr 2022.
Ahmadmehrabi S, Li B, Epstein DJ, Ruckenstein MJ, Brant JA.: How Does the "Cookie-Bite" Audiogram Shape Perform in Discriminating Genetic Hearing Loss in Adults? Otolaryngol Head Neck Surg 166(3): 527-539, Mar 2022.
Chen T, Rohacek AM, Caporizzo M, Nankali A, Smits JJ, Oostrik J, Lanting CP, Kücük E, Gilissen C, van de Kamp JM, Pennings RJE, Rakowiecki SM, Kaestner KH, Ohlemiller KK, Oghalai JS, Kremer H, Prosser BL, Epstein DJ.: Cochlear supporting cells require GAS2 for cytoskeletal architecture and hearing. Developmental Cell 56: 1526-1540, 2021.
Muthu, V., Rohacek A.M., Yao, Y., Rakowiecki,S.M., Brown, A.S., Zhao, Y.T, Myers, J., Won, K.J, Ramdas, S., Brown, C.D., Peterson, K.A., and Epstein, D.J.: Genomic architecture of Shh dependent cochlear morphogenesis. Development 146: dev181339, 2019.
Corman, T.S., Bergendahl, S. and Epstein, D.J.: Distinct temporal requirements of Sonic hedgehog signaling in development of the tuberal hypothalamus. Development 145, 2018.
Kahn, B.M., Corman, T.S., Lovelace, K., Hong, M., Krauss, R.S. and Epstein, D.J. : Prenatal ethanol exposure in mice phenocopies Cdon mutation by impeding Shh function in the etiology of optic nerve hypoplasia. Disease Models and Mechanisms 10: 29-37, 2017.