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个人简介
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.
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.
研究兴趣
论文共 175 篇作者统计合作学者相似作者
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Carlos Dominguez Gonzalez,Leslie E. Sanderson, Raffaella Depace,Guy Helman,Kaiyuan Wu,Brianna Disanza,Amy Pizzino,Johanna Schmidt,Kayla Muirhead,Joshua Bonkowsky,Ryan Taft, Nouriya Sannaa,
Molecular Genetics and Metabolismno. 4 (2024): 108328
bioRxiv the preprint server for biology (2024)
Talia Sisroe, Attila Dos Santos,Alyssa L Rippert, Christopher Gray,Cara M Skraban,Beverly Nelson, Sarah Tefft,Ingo Helbig, Dong Li,Elizabeth J Bhoj,Andrew K Sobering
American journal of medical genetics. Part App.e63816-e63816, (2024)
AMERICAN JOURNAL OF HUMAN GENETICSno. 2 (2024): 364-382
Dana E. Layo-Carris,Emily E. Lubin,Annabel K. Sangree,Kelly J. Clark,Emily L. Durham,Elizabeth M. Gonzalez, Sarina Smith,Rajesh Angireddy, Xiao Min Wang, Erin Weiss,Roberto Mendoza-Londono,Lucie Dupuis,
EUROPEAN JOURNAL OF HUMAN GENETICSno. 8 (2024): 1-10
Cell Stem Cellno. 3 (2024): 288-289
JOURNAL OF CLINICAL INVESTIGATIONno. 1 (2024)
Tomoki T Nomakuchi, Eden Y Teferedegn, Dong Li,Kayla J Muirhead,Holly Dubbs, Jacqueline Leonard,Colleen Muraresku, Emily Sergio, Kaley Arnold,Amy Pizzino,Cara M Skraban,Elaine H Zackai,
American journal of medical genetics. Part App.e63817-e63817, (2024)
Paranchai Boonsawat,Reza Asadollahi, Dunja Niedrist,Katharina Steindl,Anaïs Begemann,Pascal Joset,Elizabeth J. Bhoj, Dong Li,Elaine Zackai, Annalisa Vetro,Carmen Barba,Renzo Guerrini,
The American Journal of Human Genetics (2024)
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作者统计
#Papers: 163
#Citation: 2086
H-Index: 26
G-Index: 42
Sociability: 8
Diversity: 2
Activity: 45
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