Post-doctoral training position to investigate disease mechanisms caused by disruption of a postnatal alternative splicing regulatory network

Posted on August 9, 2023

The Tom Cooper lab at Baylor College of Medicine has open projects that investigate that investigate two related areas:  (1) the mechanisms and physiological consequences of conserved alternative splicing transitions regulated during mammalian postnatal development and (2) the disruption of this regulatory network that is the pathogenic mechanism of the microsatellite expansion disease myotonic dystrophy type 1 (DM1) that affects multiple tissues and is the most common cause of muscular dystrophy in adults. In DM1, the RNA expressed from the expanded allele disrupts regulation of a network of alternative splicing transitions that normally drive fetal to adult protein isoform expression. Expression of fetal protein isoforms unable to perform the functions required in adult tissue causes disease features. The investigations in these two areas are complementary and provide the basis for an exchange of ideas and collaboration within the lab.

We use our published and unpublished DM1 mouse models in heart, skeletal muscle, the gastrointestinal system and brain (newly initiated) as well as cell culture models for investigations of disease mechanisms. We also test therapeutic approaches including small molecules, CRISPR and antisense oligonucleotides in our lab and in collaborations with biotech companies. Representative papers:  PNAS 105, 2646; J Clin Invest 119, 3797; PNAS 110, 13570; Cell Reports 6, 336, PNAS 109, 4221, ACS Chem Biol 12, 2503; Human Mol Genet 27, 2789; J Am Heart Assoc 7, e010393., J Clin Invest Insight 6:e143465; Nucleic Acids Res 2023 10.1093/nar/gkac1219.

The study of DM1 pathogenic mechanisms identified a network of hundreds of postnatal alternative splicing transitions that occur shortly after birth, a large number of which are required for normal function. We investigate how the splicing networks are regulated and the physiological functions of selected conserved splicing transitions, particularly those disrupted in DM1. Representative papers:  PNAS 105, 20333; Genes Dev 24, 653; Nature Commun 5, 3603; Molecular Cell, 55, 592; eLife 6:e27192, Cell Reports 24, 197.

As the PI, my role is to work with each trainee to become an independent scientists and to help them reach the next step in their chosen career. I’ve mentored 40 trainees (24 pre-doc and 16 post-doc) who have gone on to a diverse range of successful independent careers in science. The success of our lab depends on our trainees and demonstrates the mutual benefits of active mentoring. See, “Previous Lab Members” on lab website for publications, grants and positions for all previous trainees.

Baylor College of Medicine is located within the Texas Medical Center (https://www.tmc.edu/), the largest medical center in the world known for its collaborative environment among basic and clinical scientists in a variety of fields and a growing biotech community (https://www.tmc.edu/innovation/innovation-programs/).

Houston is the fourth largest and most diverse city in the United States with all the amenities one would expect of a large city while being quite affordable (https://www.bcm.edu/about-us/life-in-houston).

Information about projects, lab environment, training goals, mentoring style and trainee outcomes can be found on our lab website https://www.bcm.edu/research/faculty-labs/tom-cooper-lab. Contact Dr. Tom Cooper to set up a time for a discussion at [email protected]; (713)-798-3141. Also feel free to contact individuals in the lab (contact info on lab website).