Positions

Assistant Professor
Molecular and Human Genetics
Baylor College of Medicine
Houston, Texas, United States
Assistant Professor
Genetics & Genomics Graduate Program
Baylor College of Medicine
Assistant Professor
Development, Disease Models & Therapeutics Graduate Program
Baylor College of Medicine
Academic Director
Mouse Embryonic Stem Cell Core
Baylor College of Medicine
Co-Director, Genetically Engineered Mouse Shared Resource
Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine

Education

BS from University Of New Hampshire
PhD from Pennsylvania State University
Post-Doctoral Fellowship at Case Western Reserve University

Professional Interests

  • Testicular and colon cancer genetics
  • Stem/progenitor cell maintenance
  • Mouse models of human diseases
  • Genome editing technologies

Professional Statement

In my laboratory we use mouse genetics and genomics to identify genes and pathways involved in the neoplastic transformation of stem/progenitor cells. Our overall goal is to utilize knowledge gained from our mouse models to understand the causes of tumor initiation in humans and to provide new targets for the early diagnosis and treatment of cancer. Ongoing research includes:

Characterize genes and developmental pathways that contribute to testicular germ cell tumor (TGCT) initiation.

Germ cells arise during embryogenesis as pluripotent primordial germ cells (PGCs) that differentiate into mature gametes and ultimately the cells and tissues of an adult organism. Defects during male germ cell development can lead to the formation of TGCTs. In 129 mice, TGCTs arise during embryonic days (E)13.5-15.5 as foci of pluripotent embryonal carcinoma cells (EC cells), which differentiate to form teratomas. At E13.5, male germ cells normally enter mitotic arrest until after birth and female germ cells initiate the meiotic program, both of which are accompanied by down-regulation of pluripotency. We recently identified a defect in this developmental switch as the cause of TGCT initiation. In TGCT susceptible gonads, germ cells delay entry into mitotic arrest, retain pluripotency, delay expression of male germ cell differentiation genes, and express genes associated with embryonic female germ cells. Continued expression of both pluripotency and differentiation-associated genes through E15.5 is directly related with germ cell transformation into EC cells. Ongoing studies are using genome editing in mice, whole organ culture systems, and developmental and genomic approaches to (1) characterize the mechanisms by which male germ cell specification is delayed, (2) test the contributions of delayed Nanos2 expression and aberrant Ccnd1 expression to tumor initiation, (3) characterize the mechanism by which partial deficiency for translation initiation factor Eif2-beta reduces tumor incidence, (4) test the contribution of a shift in pluripotent states (i.e. naïve to primed pluripotency) to germ cell transformation into EC cells, and (5) functionalize TGCT susceptibility loci identify in human genome-wide association studies (e.g. Prdm14).

Develop in vivo CRISPR/Cas9 genome editing technologies.

As the Director of the Mouse ES Cell Core and co-PI of the BCM component of the NIH-funded Knockout Mouse Production and Phenotyping (KOMP2) project, I oversee the project design and reagent production pipeline for in vivo CRISPR/Cas9 genome editing in mice for BCM investigators and BCM component of KOMP2. To date we have successfully generated over 400 CRISPR/Cas9 mutagenized mouse lines. Our lab is implementing several new approaches (e.g. asymmetric oligo donors, long single stranded oligo donors, and embryo electroporations) and developing novel reagents (e.g. oocyte-specific Cas9 and high fidelity Cas9 transgenic mice) to increase the efficiency and efficacy of in vivo CRISPR/Cas9 genome editing in mice.

Selected Publications

Memberships

Dan L Duncan Cancer Center
Center for Reproductive Medicine
Digestive Diseases Center

Funding

Genetic susceptibility to testicular germ cell tumors
- #RP150081
Cancer Prevention Research Institute of Texas (CPRIT)
CONSORTIUM FOR LARGE-SCALE PRODUCTION AND PHENOTYPING OF KNOCKOUT MICE (UM1)
- #UM1 HG006348
NIH/NHGRI
BCM-Rice resource for the analysis of somatic gene editing in mice
- #U42 OD026645
NIH/OD