Elizabeth Bhoj, M.D., Ph.D.

faculty photo
Assistant Professor of Pediatrics (Human Genetics)
Department: Pediatrics
Graduate Group Affiliations

Contact information
Children's Hospital of Philadelphia
Colket Translational Research Center, Room 5012
Philadelphia, PA 19104
BS (Biology and Philosophy)
The College of New Jersey, 2002.
University of Texas Southwestern Medical Center at Dallas, 2010.
PhD (Genetics)
University of Texas Southwestern Medical Center at Dallas, 2010.
MTR (Translational Research )
University of Pennsylvania, 2016.
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Description of Research Expertise

Research Interests: Our lab works in translational genetics to improve diagnosis and treatment through the discovery, mechanistic understanding, and targeted treatment of novel human syndromes.

Keywords: genetics, genomics, clinical genetics, molecular genetics, exome sequening, genome sequencing, RNAseq, gene discovery, neurogenetics, histone, mTOR, RAS, targeted therapeutics

Research Details: The motivation behind the work of the Bhoj lab is to provide answers to families about their child’s medical issues and work towards targeted therapies for genetic disorders. There are many thousands of children who are suspected to have a genetic disorder, but remain without a diagnosis, even after expert evaluation. Many of these children have yet-undiscovered genetic syndromes, and the Bhoj lab uses advanced sequencing technology to identify these novel syndromes. Two of the syndromes we now focus on are caused by disruption of Histone 3.3 (H3F3A and H3F3B) and TBC1 domain-containing Kinase (TBCK).

Histone 3.3 is one of the replacement histones, and is vital for appropriate cell division, transcription, and many other processes. Somatic variants cause a variety of cancer, including pediatric glioblastoma. Our laboratory described a pediatric neurodegenerative condition caused by germline variants in H3F3A and H3F3B, which both code for the Histone 3.3 protein. Using patient cells, mouse models, and iPSC cells, we are learning more about why these genetic variant cause this disease. Our goal is to be able to learn enough about the pathogenesis of the disorder to develop the first targeted therapies for this progressive neurologic disorder.

Our laboratory was also instrumental in the discovery of TBC1 domain-containing Kinase (TBCK) as a cause of progressive neurodegeneration in children. Very little was known about the role of TBCK, and we are working to learn more about how TBCK works in healthy tissues and contributes to neurodegeneration. We are using patient cells and model organisms to understand how the loss of this protein disrupts normal neurologic development. Our early data suggested the mTOR pathway was downregulated in these patients, and we showed that leucine, an amino acid, is a potential targeted therapy. We are now working on leucine and related compounds in animal models of the disease and hope to start a human trial.

Rotation Projects: We have rotation projects that range from improved genetic diagnostic techniques, to wet bench and animal research on furthering our understanding of some of the exciting new diseases we've discovered. Our work is driven by both basic science and translational research - and we always have an eye on targeted drug development. Specifically we have rotation projects on the role of a new disorder - TBCK-related encephalopahy and its treatment with an amino acid mixture. Also, learning more about how germline mutations in Histone 3.3 cause a progressive neurological syndrome and how we can treat these patients. We also have more than a dozen novel disorders we've found in patients and need to verify using functional data in the lab.

Lab Personnel: We currently have one MSTP (MD/PhD) student, a technician, a postdoc, a veterinary fellow, and a physician scientist in the lab.

Selected Publications

Wenger, T., Li, D., Harr, M. H., Tan, W. H., Pellegrino, R., Stark, Z., Hakonarson, H., Bhoj, E. J.: Expanding the phenotypic spectrum of TP63-related disorders including the first set of monozygotic twins. Am J Med Genet A 176(1): 75-81, 2018.

Smol, T., Petit, F., Piton, A., Keren, B., Sanlaville, D., Afenjar, A., Baker, S., Bedoukian, E. C., Bhoj, E. J., Bonneau, D., Boudry-Labis, E., Bouquillon, S., Boute-Benejean, O., Caumes, R., Chatron, N., Colson, C., Coubes, C., Coutton, C., Devillard, F., Dieux-Coeslier, A., Doco-Fenzy, M., Ewans, L. J., Faivre, L., Fassi, E., Field, M., Fournier, C., Francannet, C., Genevieve, D., Giurgea, I., Goldenberg, A., Green, A. K., Guerrot, A. M., Heron, D., Isidor, B., Keena, B. A., Krock, B. L., Kuentz, P., Lapi, E., Le Meur, N., Lesca, G., Li, D., Marey, I., Mignot, C., Nava, C., Nesbitt, A., Nicolas, G., Roche-Lestienne, C., Roscioli, T., Satre, V., Santani, A., Stefanova, M., Steinwall Larsen, S., Saugier-Veber, P., Picker-Minh, S., Thuillier, C., Verloes, A., Vieville, G., Wenzel, M., Willems, M., Whalen, S., Zarate, Y. A., Ziegler, A., Manouvrier-Hanu, S., Kalscheuer, V. M., Gerard, B., Ghoumid, J.: MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype. Neurogenetics 2018.

Hailey Pinz, Louise C. Pyle, Dong Li, Kosuke Izumi, Cara Skraban, Jennifer Tarpinian, Stephen R. Braddock, Aida Telegrafi, Kristin G. Monaghan, Elaine Zackai, Elizabeth J. Bhoj: De novo variants in Myelin regulatory factor (MYRF) as candidates of a new syndrome of cardiac and urogenital anomalies. American Journal of Medical Genetics Part A 176(4): 969-972, 2018.

Elizabeth J Bhoj, H3F3A/B Consortium, Hakon H. Hakonarson.: Mutations In H3f3a And H3f3b Encoding Histone 3.3: Report Of 26 Patients With Neurodevelopmental And Congenital Manifestations. American Society of Human Genetics, Orlando, FL October 2017 Notes: Platform Presentation.

Elizabeth J Bhoj, H3F3A/B Consortium, Hakon H. Hakonarson: Mutations In H3f3a And H3f3b Encoding Histone 3.3: Report Of 26 Patients With Neurodevelopmental And Congenital Manifestations. 38th Annual David W. Smith Workshop, Burlington, VT August 2017 Notes: Platform Presentation.

Elizabeth J Bhoj, Dong Li, Margaret H Harr, Hakon H Hakonarson: Utilization of a Craniofacial Malformation Patient Cohort to Identify Novel Syndromes Leading to Targeted Therapeutics Development. American Cleft Palate Craniofacial Association Meeting. Colorado Spring, CO March 2017 Notes: Oral Abstract Presentation.

Wenger, T.L., Bhoj, E.J.: Contemporary Evaluation of the Neonate with Congenital Anomalies. NeoReviews 18(1): e522-e531, 2017.

Kury, S., van Woerden, G. M., Besnard, T., Proietti Onori, M., Latypova, X., Towne, M. C., Cho, M. T., Prescott, T. E., Ploeg, M. A., Sanders, S., Stessman, H. A. F., Pujol, A., Distel, B., Robak, L. A., Bernstein, J. A., Denomme-Pichon, A. S., Lesca, G., Sellars, E. A., Berg, J., Carre, W., Busk, O. L., van Bon, B. W. M., Waugh, J. L., Deardorff, M., Hoganson, G. E., Bosanko, K. B., Johnson, D. S., Dabir, T., Holla, O. L., Sarkar, A., Tveten, K., de Bellescize, J., Braathen, G. J., Terhal, P. A., Grange, D. K., van Haeringen, A., Lam, C., Mirzaa, G., Burton, J., Bhoj, E. J., Douglas, J., Santani, A. B., Nesbitt, A. I., Helbig, K. L., Andrews, M. V., Begtrup, A., Tang, S., van Gassen, K. L. I., Juusola, J., Foss, K., Enns, G. M., Moog, U., Hinderhofer, K., Paramasivam, N., Lincoln, S., Kusako, B. H., Lindenbaum, P., Charpentier, E., Nowak, C. B., Cherot, E., Simonet, T., Ruivenkamp, C. A. L., Hahn, S., Brownstein, C. A., Xia, F., Schmitt, S., Deb, W., Bonneau, D., Nizon, M., Quinquis, D., Chelly, J., Rudolf, G., Sanlaville, D., Parent, P., Gilbert-Dussardier, B., Toutain, A., Sutton, V. R., Thies, J., Peart-Vissers, Lelm, Boisseau, P., Vincent, M., Grabrucker, A. M., Dubourg, C., Undiagnosed Diseases, Network, Tan, W. H., Verbeek, N. E., Granzow, M., Santen, G. W. E., Shendure, J., Isidor, B., Pasquier, L., Redon, R., Yang, Y., State, M. W., Kleefstra, T., Cogne, B., Gem, Hugo, Deciphering Developmental Disorders, Study, Petrovski, S., Retterer, K., Eichler, E. E., Rosenfeld, J. A., Agrawal, P. B., Bezieau, S., Odent, S., Elgersma, Y., Mercier, S.: De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. Am J Hum Genet 101(5): 768-788, 2017.

Bhoj, E. J., Yu, Z., Guan, Q., Ahrens-Nicklas, R., Cao, K., Luo, M., Tischler, T., Deardorff, M. A., Zackai, E., Santani, A. B.: Phenotypic predictors and final diagnoses in patients referred for RASopathy testing by targeted next-generation sequencing. Genet Med 19(6): 715-718, 2017.

Gibson, Kristin McDonald, Nesbitt, Addie, Cao, Kajia, Yu, Zhenming, Denenberg, Elizabeth, DeChene, Elizabeth, Guan, Qiaoning, Bhoj, Elizabeth, Zhou, Xiangdong, Zhang, Bo, Wu, Chao, Dubbs, Holly, Wilkens, Alisha, Medne, Livija, Bedoukian, Emma, White, Peter S., Pennington, Jeffrey, Lou, Minjie, Conlin, Laura, Monos, Dimitri, Sarmady, Mahdi, Marsh, Eric, Zackai, Elaine, Spinner, Nancy, Krantz, Ian, Deardorff, Matt, Santani, Avni: Novel findings with reassessment of exome data: implications for validation testing and interpretation of genomic data. Genet Med. American College of Medical Genetics and Genomics, 20(3): 329-33, 2017.

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Last updated: 06/27/2023
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