Date: 18 March 2026 (Wednesday)
Time: 11:00 am – 12:00 pm
Venue: Lecture Theatre 2, G/F, William M.W. Mong Block, 21 Sassoon Road 
Host: Professor Jiandong Huang

Dr. T.L. To received his Ph.D. in Chemical Engineering from the Massachusetts Institute of Technology (MIT), where he uncovered how stochastic noise in gene expression drives cell fate decisions. He then completed postdoctoral research at the University of California San Francisco (UCSF), supported by the Croucher Foundation, where he invented imaging probes for cell signaling, optogenetic tools, and protein-protein interaction assays. At the Broad Institute of MIT and Harvard, he led functional genomics efforts that produced the first comprehensive human mitochondrial chemical-genetic interaction map and a scalable screening platform linking genetics to mitochondrial bioenergetics, advancing understanding of how mitochondrial physiology shapes disease biology, including cancer. Beyond academia, Dr. To brings experience in biotechnology and drug discovery. His work lies at the intersection of chemical and systems biology, mitochondrial physiology, platform technologies for drug discovery, and translational science.

Mitochondria are central to cellular metabolism, energy production, and programmed cell death, processes that are frequently dysregulated in human conditions ranging from cancer to aging. How mitochondrial defects lead to such pleiotropic and heterogeneous pathologies remains unclear. I will discuss efforts to build a systems genetic framework for understanding mitochondrial physiology in human cells. First, I will present CRISPR modifier screens across diverse mitochondrial stressors to generate the first comprehensive human mitochondrial chemical-genetic interaction map, identifying over one hundred genetic suppressors and sensitizers of mitochondrial dysfunction and uncovering principles of intra-organelle homeostatic buffering. Second, I will introduce a platform that combines classical bioenergetic profiling with pooled CRISPR screening to systematically map the genetic determinants of membrane bioenergetics. This method, termed PMF-seq, is applied to dissect respiratory chain branching, OXPHOS reversibility, the electron transfer pathway of a novel respiratory substrate, and a new genetic sensitizer of BH3-only apoptotic signaling. Together, these complementary approaches establish a roadmap for mitochondrial function and wiring, revealing new insights that may be exploited in cancer therapy and beyond.

All are welcome.