Jaimin Patel
795,000 people suffer from stroke annually in the United States. 87% of these strokes are ischemic. This condition is a leading cause of serious long-term disability and the second leading cause of death worldwide. Current management strategies for ischemic stroke, such as alteplase treatment and mechanical thrombectomy, are focused on reperfusion of the ischemic brain regions. However, neurons continue to die even after these reperfusion therapies are instituted, leading to persistent neurological deficit. No clinically available therapeutics can prevent this phenomenon, limiting the capacity to preserve neurologic function in this patient population. As such, there is a great need to develop therapeutic strategies capable of preventing this secondary form of neurologic injury.
Ischemic stroke and Parkinson’s disease share many molecular alterations, including the downregulation of parkin, an E3 ubiquitin ligase with critical neuroprotective functions. Cytosolic substrates of parkin, such as parkin interacting substrate (PARIS), have been implicated as drivers of neurodegeneration in Parkinson’s disease. However, no study to date has examined the role of these substrates in ischemic stroke. My work, under the mentorship of Drs. Ted and Valina Dawson, has been focused on characterizing the role of PARIS in neuronal death following cerebral ischemia. We demonstrated that PARIS becomes upregulated in ischemic stroke through enhanced proteasomal degradation of parkin. Using a PARIS gene knockout mouse model, we discovered that PARIS knockout dramatically reduces infarct volume and neurological deficit following cerebral ischemia. Finally, we identified that PARIS gene knockdown attenuates both cell autonomous and non-cell autonomous modes of neuronal death using an in vitro model of cerebral ischemia. Together, our results suggest that PARIS is a promising therapeutic target in the context of ischemic stroke.
Questions & Answers
Why did you choose Johns Hopkins for your work?
My interest in Johns Hopkins began when I learned about its outstanding medical
education program and research training opportunities, particularly within the
neurosciences. However, my experience on interview day indicated the true driver of my
decision. I remember the first faculty member I met. He initiated a lengthy discussion on
my research experience, but he maintained a warm, welcoming demeanor. Throughout
the day, I continued to see members of the Johns Hopkins community uniquely exhibit
both collegiality and intellectual curiosity. I knew I wanted these traits in colleagues and
mentors, so I decided to pursue my medical education and hone my capabilities in bench
research here. I continue to experience this treatment both in the laboratory and in the
hospital, so I know I made the right decision.
What does receiving this award mean to you personally and professionally? Do you have any
connection with the particular award you received?
I am deeply honored to be receiving this award. I am grateful to be continuing the legacy
of such an influential figure within biomedical research. As the father of chemotherapy
and the mind behind the initial syphilis treatment, Dr. Paul Ehrlich was truly a pioneer in
translational research. This award will further motivate me in my pursuit of a career as a
neurosurgeon-scientist. Above all, it serves as a reminder of the high caliber mentorship
and unwavering support of my mentors, Drs. Ted and Valina Dawson. Akin to Dr.
Ehrlich, I hope to dedicate my capacity as a researcher toward developing a “magic
bullet” that protects against acute and chronic forms of neuronal death.
What contributed to your project’s success?
The outstanding mentorship of Drs. Ted and Valina Dawson has been key to the success
of this work. They inspire me daily to exercise my creativity, to innovate, and to maintain
my knowledge of the literature. Their unwavering support has enabled my persistence in
executing this study, and their guidance in study design continues to make me a better
scientist. Research associates and specialists Drs. Suyi Cao, Hu Wang, Mohammed
Repon Khan, and Rong Chen are integral members of the team who have pushed this
work forward through their expertise and guidance. The relentless support of my parents,
brother, partner and friends was essential in maintaining morale and perseverance.
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?
I believe Young Investigators’ Day is a tremendous opportunity, and I am humbled to be
a part of it. It provides a unique platform to elevate the excellent work of students and
fellows at Johns Hopkins, and it is a testament to the dedication of Johns Hopkins
toward the success of its trainees.
What has been your best/most memorable experience while at Johns Hopkins?
I remember the moment I made the foundational discovery for my current project. I had
gone through almost a year of testing ideas for potential projects to no avail. I had a
preliminary result showing that PARIS is upregulated following ischemic stroke in mice,
but I had no data showing PARIS is involved in neuronal death in this disease context. I
remember looking at the results of a pilot experiment using PARIS gene knockout mice,
which showed neuroprotection at one day following ischemia. I remember feeling
immense relief and excitement as I realized that all the hours I had spent in the laboratory
had finally produced an actionable result. Clinically, I will never forget my experiences
on the various surgery services. I have had the privilege of observing the spectrum of care
provided by surgeons, from the most complex procedures to conversations about end-of-life
considerations. Reminiscing on these experiences continually reminds me of why I
am on this career path.
What are your plans over the next year or so? Graduating, looking for faculty positions, etc.?
I plan to finish my year of research this summer and my fourth year of medical school in
May of 2025. I will be applying to residency positions in neurological surgery beginning
this fall.
Tell me something interesting about yourself that makes you unique. Do you have any special
hobbies, interests or life experiences?
I enjoy outdoor activities, such as hiking, fishing and camping. My favorite hike is called
Angel’s Landing in Zion National Park. The hike is difficult, but the view at the top is
unmatched. As a result of my partner, I have recently come to appreciate trails in the
DMV, such as Annapolis rock and the Old Rag trail at Shenandoah National Park.