Northwestern University

Jan
29
Mon 4:00 PM

Research Works-in-Progress: Valery Adorno-Cruz and Dina Simkin, Ph.D.

When: Monday, January 29, 2018
4:00 PM - 5:00 PM  

Where: Ward Building, 5-230, 303 E. Chicago Avenue, Chicago, IL 60611 map it

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

Contact: Liz Barrera Murphy   312.503.4892

Group: Department of Pharmacology Seminars

Category: Lectures & Meetings

Description:

Please join the Department of Pharmacology for a Works-in-Progress presentation.

Valery Adorno-Cruz, Graduate Student in the Laboratory of Dr. Huiping Liu

"Integrin α2 promotes metastasis of triple negative breast cancer"

Integrins are the main receptors that bind the cells to the extracellular matrix and they have been found to have roles in cancer migration, altering metastasis and even considered as stemness markers. They form heterodimers composed of different alpha and beta subunits, forming 24 known combinations. Despite the recognition of integrin beta1 subunit (which can form heterodimers with multiple alpha subunits) as a stemness marker in breast cancer and other cancers, the role of one of its binding subunit, α2 is not particularly understood. My work using triple negative cells lines and PDX models reveals that knocking down high levels of integrin reduces lung colonization in vivo, contributed by altered cell cycle, migration and invasion as well as slightly changed cell viability as found in vitro.

Dina Simkin, Ph.D., Postdoctoral Fellow in the Laboratory of Dr. Alfred George

"Neurophysiological mechanisms of KCNQ2 epileptic encephalopathy"

Neonatal epileptic encephalopathy (NEE) is a complex disorder that manifests as severe early-onset seizures and developmental deficits due to an imbalance in neuronal circuit activity in the brain1,2. NEE can be caused by heterozygous missense mutations in the KCNQ2 gene, which encodes the voltage-gated potassium channel KCNQ2 (Kv7.2) responsible for neuronal M-current3. NEE begins during critical stages of development, when cortical neurons and networks are still maturing. While studies of channelopathies using heterologous expression systems and mouse models have been informative, the specific mechanisms by which developmental expression of KCNQ2 channels impact neuronal excitability are not clear. Further, the functional roles and cell type-specific distribution of orthologous channels differ between mice and humans4-6. Hence, there is a fundamental need to develop more human-relevant model systems for epilepsy to bridge the gap between studies in animal models and human clinical presentation of epileptic disorders.
The use of patient-specific induced pluripotent stem cells (iPSCs) has enabled a new approach for elucidating pathogenic mechanisms of genetic disorders such as the epileptic channelopathies as it allows for the generation of otherwise inaccessible human neurons. In collaboration with pediatric epileptologists at Lurie Children’s Hospital, we have generated iPSCs from several genetic-epilepsy patients, from which we further generated isogenic control iPSCs using CRISPR-Cas9 gene editing. My work addresses how stable mutations in KCNQ2 affect: 1) the rate and efficiency of neuronal maturation during critical developmental periods and 2) intrinsic and network excitability in specific neuronal subtypes to determine if dyshomeostatic changes drive network hyperexcitability and the severity of disease.

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