Northwestern Events Calendar

Jan
25
2021

Research Works in Progress: Davi Leite, PhD and Nicole Hawkins, PhD

When: Monday, January 25, 2021
4:00 PM - 5:00 PM Central

Where: Online

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Liz Murphy   312.503.4892

Group: Department of Pharmacology Seminars

Category: Lectures & Meetings

Description:

Davi Lyra-Leite, PhD
Postdoctoral Fellow in the Laboratory of Paul Burridge, PhD

"Advances in protein-free differentiation of human induced pluripotent stem cell-derived cardiomyocytes"

Abstract: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have established roles in modeling human disease, pharmacogenomics, drug testing/discovery, and regenerative medicine. However, the majority of cardiac differentiation protocols still rely on the use of animal protein and/or sera to obtain high yield functional tissue monolayers. This increases costs and variability of the differentiation process, while introducing potential xenographic effects that limit regenerative medicine applications. Over the past year, we employed a systematic analysis of media compositions to develop a novel protein-free cardiac differentiation protocol that produces high purity functional monolayers with small impact in hiPSC-CM yield at a fraction of standard protocol cost. This process has also highlighted a number of intriguing mechanistic questions regarding the basic chemical/nutritional requirements for human cardiac development that we have been further exploring.

Nicole Hawkins, PhD
Research Assistant Professor of Pharmacology

"Gabra2 is a genetic modifier of Dravet syndrome in mice"

Pathogenic mutations in epilepsy genes result in a spectrum of clinical presentation likely due to modifier genes that affect penetrance, dominance or expressivity of the variant. The Scn1a+/- model of Dravet syndrome, a severe epilepsy, displays varying severity. 129.Scn1a+/- mice have a normal lifespan and no seizures, while F1[B6x129].Scn1a+/- mice have severe epilepsy and premature death. Gabra2, encoding the GABAA α2 subunit, was nominated as one modifier gene. Previous work identified lower levels of α2 in hippocampal synapses in B6 mice and a B6-specific single nucleotide intronic deletion. We utilized repaired Gabra2 B6 mice to validate its modifier effects in Scn1a+/- mice, which restored α2 expression and improved Scn1a+/- phenotypes. 

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