Nicholas J. Hand, Ph.D.
Research Assistant Professor of Genetics
Department: Genetics
Contact information
11-135 Smilow Center for Translational Research
Philadelphia, PA 19104-5156
Philadelphia, PA 19104-5156
Email:
njhand@upenn.edu
njhand@upenn.edu
Publications
Education:
BA (Genetics)
Trinity College, Dublin 2, Ireland, 1992.
Ph.D. (Molecular Biology (Mentor: Tom Silhavy))
Princeton University, 2002.
Permanent linkBA (Genetics)
Trinity College, Dublin 2, Ireland, 1992.
Ph.D. (Molecular Biology (Mentor: Tom Silhavy))
Princeton University, 2002.
Description of Research Expertise
Dr Hand is a broadly trained molecular biologist with a long-standing interest in the diseases that affect, or have their origins in, the liver, and in microRNAs with regulatory roles in liver development, physiology, and disease.His work is informed by discoveries derived from cutting-edge human genetics approaches and involves the use of disease-relevant cell types derived from human induced pluripotent stem cells (iPSC), CRISPR/Cas9 genome-editing, mouse models, and primary and transformed cell lines, as well as next generation sequencing approaches to study gene expression.
Under the umbrella of his affliation with the Rader lab, Dr Hand's ongoing interests include cardiometabolic disease, metabolically-associated steatotic liver disease, and pleiotropic human loci that impact lipid and lipoprotein metabolism. His leadership within the group involves directing the functional follow up of discoveries from genome-wide and phenome-wide association studies to link variants to genes, and genes to functions.
His independent group is focussed on cholestatic liver disease, and diseases of haploinsufficiency, with a particular interest in mRNA regulatory elements as targetable axes to treat a variety of haploinsufficient conditions.
Selected Publications
KT Creasy, MB Mehta, CV Schneider, J Park, D Zhang, SV Shewale, JS Millar, M Vujkovic, NJ Hand, PM Titchenell, JA Baur, and DJ Rader: Ppp1r3b is a metabolic switch that shifts hepatic energy storage from lipid to glycogen. Science Advances Accepted for publication, 2025.Farica Zhuang, Danielle Gutman, Nathaniel Islas, Bryan B Guzman, Alli Jimenez, San Jewell, Nicholas J Hand, Katherine L Nathanson, Daniel Dominguez, Yoseph Barash: G4mer: An RNA language model for transcriptome-wide identification of G-quadruplexes and disease variants from population-scale genetic data. bioRXiv 10(1): 616124, Oct 2024 Notes: https://www.biorxiv.org/content/10.1101/2024.10.01.616124v1.
HYR Huang, C Vitali, D Zhang, NJ Hand, MC Phillips, KT Creasy, E Scorletti J Park, Regeneron Centre, KM Schneider, DJ Rader, CV Schneider: Deep metabolic phenotyping of humans with protein-altering variants in TM6SF2 using a genome-first approach. JHEP Reports. Elsevier, 7(1): 101243, Oct 2024 Notes: 10.1016/j.jhepr.2024.101243.
Nicholas J. Hand: A Nutraceutical Mechanistic Model Receives a Gut Check. Cellular and Molecular Gastroenterology and Hepatology Page: doi: 10.1016/j.jcmgh.2024.02.007. Feb 2024.
Eleonora Scorletti, Yedidya Saiman, Sookyoung Jeon, Carolin V Schneider, Delfin G Buyco, Chelsea Lin, Blanca E Himes, Clementina A Mesaros, Marijana Vujkovic, Kate Townsend Creasy, Emma E Furth, Jeffrey T Billheimer, Nicholas J Hand, David E Kaplan, Kyong-Mi Chang, Philip S Tsao, Julie A Lynch, Joseph L Dempsey, Julia Harkin, Susovon Bayen, Donna Conlon, Marie Guerraty, Michael C Phillips, Daniel J Rader, Rotonya M Carr: A Missense Variant in Human Perilipin 2 (Plin2 Ser251pro) Reduces Hepatic Steatosis In Mice. JHEP Reports Page: 100902, Oct 2023.
Creasy, K.T., Mehta, M., Park, J., Schneider, C.V., Shewale, S., Millar, J.S., Hand, N.J., Baur, J.A. and Rader, D.J.: PPP1R3B is a metabolic switch that shifts hepatic energy storage from lipid to glycogen. bioRXiv 2023(3): doi.org/10.1101/2023.03.04.529958, Mar 2023.
Stankov S, Vitali C, Park J, Nguyen D, Mayne L, Englander SW; Regeneron Genetics Center; Levin MG, Vujkovic M, Hand NJ, Phillips MC, Rader DJ.: Comparison of the structure-function properties of wild-type human apoA-V and a C-terminal truncation associated with elevated plasma triglycerides. medRxiv Feb 2023.
Larsen LE, van den Boogert MAW, Rios-Ocampo WA, Jansen JC, Conlon D, Chong PLE, Levels JHM, Eilers RE, Sachdev VV, Zelcer N, Raabe T, He M, Hand NJ, Drenth JPH, Rader DJ, Stroes ESG, Lefeber DJ, Jonker JW, Holleboom AG.: Defective Lipid Droplet-Lysosome Interaction Causes Fatty Liver Disease as Evidenced by Human Mutations in TMEM199 and CCDC115. Cellular and Molecular Gastroenterology and Hepatology 13(2): 583-597, Oct 2022.
Bi X, Stankov S, Lee PC, Wang Z, Wu X, Li L, Ko YA, Cheng L, Zhang H, Hand NJ, Rader DJ.: ILRUN Promotes Atherosclerosis Through Lipid-Dependent and Lipid-Independent Factors. Arterioscler Thromb Vasc Biol 42(9): 1139-1151, July 2022.
Vujkovic M, Ramdas S, Lorenz KM, Guo X, Darlay R, Cordell HJ, He J, Gindin Y, Chung C, Myers RP, Schneider CV, Park J, Lee KM, Serper M, Carr RM, Kaplan DE, Haas ME, MacLean MT, Witschey WR, Zhu X, Tcheandjieu C, Kember RL, Kranzler HR, Verma A, Giri A, Klarin DM, Sun YV, Huang J, Huffman JE, Creasy KT, Hand NJ, Liu CT, Long MT, Yao J, Budoff M, Tan J, Li X, Lin HJ, Chen YI, Taylor KD, Chang RK, Krauss RM, Vilarinho S, Brancale J, Nielsen JB, Locke AE, Jones MB, Verweij N, Baras A, Reddy KR, Neuschwander-Tetri BA, Schwimmer JB, Sanyal AJ, Chalasani N, Ryan KA, Mitchell BD, Gill D, Wells AD, Manduchi E, Saiman Y, Mahmud N, Miller DR, Reaven PD, Phillips LS, Muralidhar S, DuVall SL, Lee JS, Assimes TL, Pyarajan S, Cho K, Edwards TL, Damrauer SM, Wilson PW, Gaziano JM, O'Donnell CJ, Khera AV, Grant SFA, Brown CD, Tsao PS, Saleheen D, Lotta LA, Bastarache L, Anstee QM, Daly AK, Meigs JB, Rotter JI, Lynch JA; Regeneron Genetics Center; Geisinger-Regeneron DiscovEHR Collaboration; EPoS Consortium; VA Million Veteran Program; Rader DJ, Voight BF, Chang KM.: A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation. Nat Genet 54(6): 761-771, June 2022.