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2017 Postdocs at the Interface

Stanford ChEM-H solicited seed grant proposals from the Stanford community of postdoctoral fellows for exploratory projects that align with the Institute’s mission. Successful proposals combined the complementary expertise of two or more postdoctoral researchers (including Ph.D. holders, M.D. residents and M.D. clinical fellows) seeking to collaboratively explore a potentially transformative new idea with the support of their mentors. The four proposals selected were each funded with $50,000 for one year.

"Wireless Monitoring of Blood Flow Using Biodegradable and Flexible Pressure Sensors"

Postdoctoral Scholars:

Levent Beker, Bao Lab
Yukitoshi Kaizawa, Fox and Chang Labs

Mentors:

Zhenan Bao, Chemical Engineering
Paige Fox, Plastic Surgery
James Chang, Plastic Surgery

Project Summary:

An increasing number of patients need surgical interventions that require small vessel anastomoses, which are critical to surgical success. However, current methods of monitoring blood flow post-anastomosis require trained medical staff and/or specialized equipment. Because of the lack of continuous monitoring, often times, graft failure is not noted until the opportunity to save the graft has passed. We propose a wireless blood flow measurement method that does not require trained medical staff or expensive equipment. The planned method utilizes a simple, flexible, and biodegradable sensor that will allow surgeons to monitor blood flow across vascular anastomoses continuously after surgery which would lead to less morbidity. Additionally, it could eliminate monitoring tests, decrease frequent subjective human evaluations, and limit time consuming clinic visits. In this study, a pressure sensor to detect expansion of an artery will be fabricated, and in-vivo tests will be conducted to verify the operation of the sensor. The sensor will be designed to send data wirelessly via inductive coupling and operate without battery due to its passive structure. Outcomes of this research can also be expanded to other medical applications such as treatment of brain aneurysms.


"Identifying Medically and Therapeutically Relevant GPCR Genetic Variants Based on 500,000 Patients"

Postdoctoral Scholars:

Christopher DeBoever, Bustamante Lab
A. J. Venkatakrishnan, Dror and Kobilka Labs

Mentors:

Carlos Bustamante, Biomedical Data Science, Genetics
Ron Dror, Computer Science
Brian Kobilka, Molecular & Cellular Physiology

Project Summary:

About three in five American adults take prescription drugs every month and many experience adverse drug reactions or reduced treatment efficacy. Nearly one-third of all FDA-approved drugs target ~100 G protein-coupled receptors (GPCRs), a family of proteins embedded in the cell membrane. Inherited genetic variants are known to affect disease risk and drug response, yet little is known about variants in GPCRs. Which genetic variants in GPCRs are associated with disease and diversity in drug response? What is the mechanism through which genetic variants in GPCRs affect health and drug response? We propose to answer these questions by identifying genetic variants that are associated with disease or adverse drug responses using data from 500,000 patients and studying the effect of these variants using protein structure-based modeling. Our cross-discipline approach will identify high-confidence genetic variants in GPCRs that can be used to understand the limitations of current drugs, develop new drugs, and ultimately improve patient care.


"Examining the Role of Neuron-Glia Signaling in Pain Perception"

Postdoctoral Scholars:

Erin Elizabeth Gray, Du Bois Lab
Husniye Kantarci, Zuchero Lab

Mentors:

Justin Du Bois, Chemistry
Brad Zuchero, Neurosurgery

Project Summary:

Chronic pain affects millions of people worldwide, but many existing therapeutic treatments exhibit limited efficacy or serious side effects. To improve the treatment of pain, a deeper understanding of the complex mechanisms that underlie nociception is necessary. The electrical impulses generated in response to noxious stimuli are conducted in excitable cells by voltage-gated sodium channels (NaVs). Although the excitability of neurons is thought to be controlled intrinsically, we have recently discovered that sensory neurons require signaling from myelinating glia to maintain excitability. This proposal seeks to elucidate the underlying mechanism(s) by which glia-derived molecules modulate NaV activity. Our studies will capitalize on methods developed in the Du Bois and Zuchero groups, including novel molecular probes for labeling and imaging NaVs and state-of-the-art techniques for purifying neurons and glia. Further mechanistic insight into this regulatory pathway will inform our understanding of neuronal excitability and may lead to the identification of new pharmaceutical targets for the treatment of pain.


"Identification of Biased Positive Allosteric Modulators of Cannabinoid Receptor Type 1 for the Treatment of Neuropathic Pain"

Postdoctoral Scholars:

Kaavya Krishna Kumar, Kobilka Lab
Angel Resendez, Malhotra Lab

Mentors:

Brian Kobilka, Molecular & Cellular Physiology
Sanjay Malhotra , Radiation Oncology, Radiology

Project Summary:

Neuropathic pain is a debilitating form of chronic pain caused by damage or disease to the nervous system. It is estimated to affect 1 in every 10 adults over the age of 30 and exacts a significant healthcare cost, rehabilitation and lost worker productivity. In addition, neuropathic pain places an enormous financial and emotional burden on patients and their families. Neuropathic pain remains a significant clinical problem because it responds poorly to the available therapies. Hence there is a need to identify novel analgesic targets for drug development. Evidence for the use of Cannabis sativa as a treatment for pain can be traced back to the beginnings of recorded history. It acts through the stimulation of the cannabinoid type 1 receptor (CB1R), one of the most abundantly expressed G protein-coupled receptors (GPCRs) in the central nervous system. Targeting CB1R has huge therapeutic potential in the treatment of neuropathic pain, however, psychotropic side effects preclude the widespread use of cannabinoid drugs. This proposal aims to identify molecules that would allow CB1R to preferentially signal via pathways that cause pain relief without the side effects. The outcomes of this proposal will have profound implications in the treatment and management of neuropathic pain.