CBG Leaders Afield: Jai Pandey at MIT

Jai Pandey is a fellow at the prestigious Whitehead Institute at the Massachusetts Institute of Technology (MIT). He recently reached out and was generous enough to sit down to speak with us about life, science, and how his professional ambitions align with the mission of the Carolina Biotech Group. 

Tell us something interesting about yourself that most people might not know?

I like watching documentary movies.

CBG is devoted to building a professional network of leaders like yourself in science, engineering, and medicine.  In turn we hope to provide high impact opportunities to our alumni, future bioentrepreneurs, and leaders from our area.  You contacted us about interest in the group, what interests you most about what CBG is doing and how can we help leaders like yourself?

CBG is doing a great job with a focus of developing biotech sector in South Carolina. I think CBG is a good platform for scientists like myself to participate actively towards the common goal.

What brought you to USC’s program and how do you feel about the network and your level of connectivity since moving on to greener fields?

I finished my Masters degree in biotechnology before joining USC’s Biology PhD program. The interdisciplinary nature of program really attracted me towards itself.

How did USC's graduate program help prepare you for the next step in your career?

I learnt various skills including performing cutting edge science and to presenting my data to audience of diverse background.  This really helped me in becoming a better scientist.

Are there any areas where you think the graduate programming could improve?

One thing I would like to say is that future of science lies in collaboration, the program should entertain more collaborative science.

You were very excited about Carolina Biotech Group and reached out to us. How do you think an organization like CBG could have been beneficial do your professional development while at USC?

 I think by  [joining] I would have gained better business insight and entrepreneurial skills which is rare to find while doing basic science in an academic set up.

One thing I would like to say is that the future of science lies in collaboration, any program should entertain more collaborative science.

Let’s talk a little bit more about your time and research at USC:  You studied Lisencephaly in Deanna Smith’s lab at USC, can you tell us a bit more what Lisencephaly is and what interested you in that project?

I studied a protein Lis1, which is involved in neural stem cell differentiation during early brain development. In the developing brain, it regulates cell division of stem cells and migration of newly formed neurons. Mutations in Lis1 cause childhood epilepsy and the condition known as, Lissencephaly. I investigated how Lis1 deficiency perturbs function in post-mitotic mature neurons. I discovered that Lis1 regulates how organelles are transported within the cell, and found that mutations in Lis1 lead to defective transport in mature neurons, which is the major cause for neurodegeneration and epilepsy. The work was published in the Journal of Neuroscience and was very well received by the scientific community, leading to an invited talk at the Society for Neuroscience annual conference.

You published your thesis work in the Journal of Neuroscience on the role of Dynein and CDK5, can you tell us a bit more about that work, it’s novelty, and whether it lends itself to any potential for therapeutic development in better understanding neurologic conditions?

During my graduate work, I investigated how neuronal function is perturbed in the rare pediatric epilepsy known as Lissencephaly. I discovered that Lis1 (a protein mutated in Lissencephaly) and CDK5 (active only in post mitotic neurons) regulates how organelles are transported within the cell. Mutations in Lis1 lead to defective transport in mature neurons, which is the major cause for neurodegeneration and epilepsy.

What are you up to now at Whitehead institute?

As a postdoc at the Whitehead Institute of MIT, I have led two projects directly related to fundamental aspects of cancer biology. The first project focused on understanding how cells maintain protein homeostasis (proteostasis) by regulating the expression of “molecular chaperones”. Many malignant cancer cells are dependent on the master regulator of proteostasis, Heat Shock Factor 1 (HSF1), to sustain rapid growth in the presence of driver and passenger mutations. I used CRISPR/Cas9 genome editing in healthy stem cells to disrupt HSF1, which led to novel insights into a possible therapeutic window for targeting the proteostasis network in cancer. A manuscript detailing the findings of this study has been accepted in Molecular Cell.

In the second project, I am leading the experimental interrogation of “allosteric hotspots” on the surface of kinases to understand how disease-associated mutations can unlock latent regulatory potential to hijack signaling pathways. In collaboration with computational biologists at UT Southwestern, we have developed new theoretical and experimental tools to predict and validate the consequences of cancer-associated mutations. We are finalizing a manuscript detailing these findings to submit to a high impact journal, and I have been invited to give a talk to present this work at 10th Annual q-bio Conference in Nashville, TN, in July.

You’ve studied neurodevelopment and cellular reprogramming, what do you think the outlook is for these fields to translate to tissue engineering and neurotechnologies?

(1) use induced pluripotent stem cells (iPSCs) culture systems for large-scale chemical and genetic screens to identify novel biomarkers for early detection and therapeutic intervention; (2) use CRISPR/Cas9 genome engineering methods to improve the safety and efficacy of gene therapy approaches.

What’s next for you?

A career in regulatory science will fulfill my passion for science and my intention to improve and safeguard human health.