Email

heaney@bcm.edu

Positions

Associate Professor

Molecular and Human Genetics
Baylor College of Medicine

Member

Genetics & Genomics Graduate Program
Baylor College of Medicine

Member

Development, Disease Models & Therapeutics Graduate Program
Baylor College of Medicine

Director

Center for Precision Medicine Models
Baylor College of Medicine

Academic Director

Genetically Engineered Rodent Models (GERM) Core
Baylor College of Medicine

Co-Leader, Advanced in Vivo Cancer Models Shared Resource

Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine

Member

Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine

Vice-Chair

International Mouse Phenotyping Consortium

Addresses

Department of Molecular and Human Genetics (Office)

Baylor College of Medicine
Houston, TX 77030
United States

Education

BS from University Of New Hampshire

01/1998 - Durham, NH United States

PhD from Pennsylvania State University

01/2004 - Hershey, PA United States

Post-Doctoral Fellowship at Case Western Reserve University

01/2010 - Cleveland, OH United States

Professional Interests

• Germ cell developement and cancer
• Mammalian genetics
• Mouse models of human diseases
• Genome editing technologies

Professional Statement

In my laboratory we use mouse genetics, genomics and genome editing technologies to catalog gene function and contribution to human disease. Ongoing research includes:

Characterizing genes and developmental pathways that contribute to testicular germ cell tumors (TGCTs). Germ cells first arise during embryogenesis as pluripotent-like cells. In the developing testis, somatic cells induce differentiation of these primordial germ cells to a unipotent spermatogonial stem cell fate. Using mouse models, we have shown that disruption of this sex-specific differentiation event causes the formation of TGCTs. Ongoing studies are using genome editing in mice, developmental biology approaches and single-cell RNA sequencing to (1) characterize the mechanisms by which male germ cell sex-specific differentiation is disrupted, (2) test the contribution of a shift in pluripotent states (i.e. naïve to primed pluripotency) to germ cell transformation into tumor stem cells and (3) functionalize TGCT susceptibility loci identify in human genome-wide association studies.

Identifying the function of protein-coding genes in the mouse genome. The Knockout Mouse Phenotyping Program (KOMP2), as a part of the International Mouse Phenotyping Consortium (IMPC) has established an infrastructure for high-throughput generation of null alleles and broad-based, adult phenotyping of knockout mouse lines. KOMP2 has also implemented embryo phenotyping pipelines for null alleles that cause lethality in the homozygous (recessive) state. KOMP2 is currently piloting a pipeline that uses (1) bioinformatics to predict genes that are haplo-essential, i.e. cause lethality in the heterozygous (dominant) state, and (2) CRISPR/Cas9 genome editing in mouse embryos, time-lapsed imaging of cultured, pre-implantation stage embryos and imaging of post-implantation stage embryos, and high-throughput embryo genotyping to characterize developmental defects associated with heterozygous loss-of-function.

Developing and employing reporter mouse strains to evaluate new genome editing delivery systems. Delivery of genome editing systems such as CRISPR/Cas9 to somatic tissues has the potential to treat or cure some of the most severe human diseases. However, there are significant challenges, including identification of delivery systems for specific tissues and evaluation of overall efficacy and safety, that must be addressed. The Somatic Cell Genome Editing (SCGE) Program is a trans-NIH initiative addressing key barriers to the therapeutic use of somatic genome editing in humans. As part of this effort, The BCM-Rice Small Animal Testing Center is creating mouse models for in vivo reporting of somatic genome editing efficiency and using these reporter strains to evaluate novel genome editing delivery systems developed by member of the SCGE.

Characterizing gene and variant contribution to Mendelian diseases. Up to 70% of patients with suspected genetic disease remain undiagnosed likely because their disease-causing variant(s) has yet to be discovered or the clinical significance of identified variants remains unclear. Precision model organisms are important tools aiding in the interpretation of these variants of uncertain clinical significance and are critical for testing therapeutic paradigms. The Center for Precision Medicine Models leverages the expertise, infrastructures and established collaborations between the Mendelian disease clinical and gene discovery programs; animal modeling programs; and database infrastructure programs within the Department of Molecular and Human Genetics. The Center supports local, national and international programs and individual researchers in the development of precision models that will end the diagnostic odyssey of patients with undiagnosed, rare and Mendelian diseases and serve as resources for pre-clinical studies investigating personalized medicine approaches to their care.

Websites

Selected Publications

• Liang SQ, Walkey CJ, Martinez AE, Su Q, Dickinson ME, Wang D, Lagor WR, Heaney JD, Gao G, Xue W "AAV5 delivery of CRISPR/Cas9 supports effective genome editing in mouse lung airway." Mol Ther. 2022;30(1):238-243. Pubmed PMID: 34695545
• Rana N, Privitera G, Kondolf HC, Bulek K, Lechuga S, De Salvo C, Corridoni D, Antanaviciute A, Maywald RL, Hurtado AM, Zhao J, Huang EH, Li X, Chan ER, Simmons A, Bamias G, Abbott DW, Heaney JD, Ivanov AI, Pizarro TT "GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis." Cell. 2022;185(2):283-298.e17. Pubmed PMID: 35021065
• Webster NJ, Maywald RL, Benton SM, Dawson EP, Murillo OD, LaPlante EL, Milosavljevic A, Lanza DG, Heaney JD "Testicular germ cell tumors arise in the absence of sex-specific differentiation." Development. 2021;148(9):dev197111. Pubmed PMID: 33912935
• Saha K, Sontheimer EJ, et al. "The NIH Somatic Cell Genome Editing program." Nature. 2021;592(7853):195-204. Pubmed PMID: 33828315

Memberships

International Mammalian Genome Society

Member

Genetics Society of America

Member

International Society for Transgenic Technology

Member

Society for the Study of Reproduction

Member

Funding

BCM Knockout Mouse Production and Phenotyping Project - #UM1 HG006348

NIH/NHGRI

BCM-Rice resource for the analysis of somatic gene editing in mice - #U42 OD026645

NIH/OD

BCM Center for Precision Medicine Models - #U54 OD030165

NIH/OD

BCM/Rice Genome Editing Testing Center - #U42 OD035581

NIH/OD