2023 ICTP Prize

The ICTP Prize is awarded every year to scientists who are from and work in developing countries, to recognise their original and outstanding contributions to theoretical physics. The winners of the 2023 ICTP Prize are Mohit Kumar Jolly of the Indian Institute of Science (IISc) in Bangalore, India, and Xinan Zhou of the Kavli Institute for Theoretical Sciences (KITS), University of Chinese Academy of Sciences (UCAS), Beijing, and ShanghaiTech University, China.

Kumar Jolly and Xinan visited ICTP to attend the ICTP Prize ceremony that took place on Wednesday 28 August 2024. On that occasion, they agreed to answer a few questions about their work and what this award means to them.

Mohit Kumar Jolly has been awarded the ICTP Prize for his innovative contributions to understanding cell dynamics in cancer metastasis and resistance to treatment. In this interview, he explains the science behind the award, what drew him to studying the biology of cancer and the main discoveries he looks forward to in his field.

How would you summarize the contributions that earned you the ICTP Prize to someone who is not in your field?

Cancer metastasis -- the spread of cancer cells from one organ to another -- and drug resistance remain major unsolved clinical challenges. But their dynamics are poorly understood, preventing fundamental insights about these processes and how to treat metastatic drug-resistant cancer. Our work unravels the crucial role that reversible bidirectional cell-state transitions play in driving these processes, by investigating them as complex adaptive systems. Our mathematical models of biochemical networks in cancer cells produced predictions that have been validated experimentally in multiple cancer types over the past decade, and can explain clinical observations, thus elucidating how cancer cells maximize their fitness during metastasis. In such interdisciplinary work, done in close collaboration with experimental cancer biologists and clinicians, our approach is to integrate the ‘first principles’ based mathematical modeling with high-dimensional experimental and clinical data to tackle cutting-edge biomedical research problems.

What new mathematical and computational methods have you developed along the way?

We have investigated the dynamics of metastasis from a nonlinear dynamics perspective, and we found multiple co-existing cell-states, called phenotypes, among which cells could transition reversibly under the influence of environmental signals and underlying stochasticity in biological processes.    We also connected the high-dimensional experimental data for these cell-state transitions with our model predictions through different statistical approaches and by reducing the data dimensionality.

What attracted you to studying the biology of cancer?

I worked on mathematical modeling in cell polarity in my Masters’ thesis at IIT Kanpur, India. In the summer of 2012, right before I started my PhD at Rice University, I came across the book ‘The Emperor of All Maladies’ by cancer doctor Siddharth Mukherjee, and was surprised to learn how little had been done to discern the systems-level dynamics of cancer, despite an increasing burden of the disease all around the world. During my PhD, I started working on modeling the dynamics of biochemical networks engaged in cancer metastasis with Prof. Herbert Levine, Prof. Jose Onuchic and the late Prof. Eshel Ben-Jacob at the Center for Theoretical Biological Physics (CTBP), where we made some initial predictions. I initiated collaborations with various experimental cancer biology groups and clinicians to test our predictions and collect more time-course experimental data on these cell-state transitions that I mentioned earlier. Many of those exciting collaborations continue today.

How can physics and mathematics help us fight cancer?

Physics and mathematics are already contributing more and more to help us fight cancer both in academic and industrial settings, for instance, in designing ‘digital twins’ of the tumors (in silico simulators for different therapeutic trials), optimizing treatment dosing strategies especially for radiotherapy, and for serving as a platform to identity combinatorial and/or sequential therapies. My group received a philanthropic grant last year to set up the Param Hansa Center for Computational Oncology at the Indian Institute of Science (IISc) Bangalore whose aim is to form and nurture an active community of future leaders in computational oncology in India, through inter-institutional, cross-disciplinary collaborations among experts in academia, medicine and industry. We are conducting workshops all over India and summer programs for students across disciplines and career stages (BS, MS, PhD) to meet our translational goal of eventually improving patient outcomes in the clinic.

What are you looking forward to as the next or the most urgent discovery in the biology of cancer?

I am very optimistic about different forms of cancer immunotherapy driving the next wave of major advances in cancer biology and eventually in clinical management of the disease.

What does the ICTP Prize mean to you?

I am so humbled and honoured to receive the ICTP Prize as a recognition of all our efforts we have put in to dissect the intricacies of cancer metastasis from a theoretical (bio-)physics perspective. This year’s prize being in honour of Sir Robert M. May makes it more special, as his seminal work on theoretical ecology was crucial in motivating me to study biological systems from a physics lens. I am also grateful that this year’s prize recognizes the growing field of biophysics and hope that it contributes to opening new opportunities for young aspiring biophysicists in developing countries.