Thomas Graham grew up in Chicago, IL and received his B.S. in Chemistry and Biological Sciences at the University of Chicago. After spending a year as a Churchill Scholar at the University of Cambridge, Thomas did his PhD in Systems Biology at Harvard University in the labs of Joe Loparo and Johannes Walter. Using single-molecule imaging in Xenopus egg extract, he discovered a two-step pathway by which broken DNA ends are brought together to be repaired by non-homologous end joining. He briefly ventured into neuroscience as a postdoc in Vanessa Ruta’s lab at Rockefeller University, before returning to his molecular roots as a postdoc with Robert Tjian and Xavier Darzacq at UC Berkeley. There he discovered proximity-assisted photoactivation (PAPA), a powerful new way to detect interactions between single pairs of molecules in live cells.

Thomas joined the Jenkins Department of Biophysics as an Assistant Professor in July 2025, where his lab will continue developing live fluorescence imaging approaches to study molecular biology.

Transcription and other cellular processes require the assembly of large consortia of biomolecules in the right place at the right time. Altering these molecular interactions can cause—or treat—disease. The Graham Lab is motivated by a simple idea: To understand molecular biology, it is crucial to know how molecules interact in their natural environment in live cells.

The Graham Lab approaches this challenge using fluorescence imaging. We have pioneered proximity-assisted photoactivation (PAPA), a method that relies on exciting a “sender” fluorophore to reactivate a nearby “receiver” fluorophore from a photochemical dark state, thereby revealing interactions between labeled molecules. Combining PAPA with fast single-molecule tracking (SMT) has allowed us to visualize individual endogenous molecular complexes in live cells for the first time. We are continuing to develop and apply PAPA, SMT, and other live fluorescence imaging approaches across various experimental systems to understand how dynamic molecular assemblies regulate transcription.

Google Scholar: https://scholar.google.com/citations?user=s0-PoxkAAAAJ&hl=en&oi=ao

Proximity-assisted photoactivation (PAPA) and single-molecule tracking (SMT)

Collective unstructured interactions drive chromatin binding of transcription factors. Abidi AA, Dailey GM, Tjian R, Graham TGW. bioRxiv [Preprint]. 2025 May 23:2025.05.16.654615. doi: 10.1101/2025.05.16.654615. PMID: 40463169

Single-molecule live imaging of subunit interactions and exchange within cellular regulatory complexes. Graham TGW, Dugast-Darzacq C, Dailey GM, Weng B, Darzacq X, Tjian R. 2025. Molecular Cell, in press

Detecting molecular interactions in live-cell single-molecule imaging with proximity-assisted photoactivation (PAPA). Graham TGW, Ferrie JJ, Dailey GM, Tjian R, Darzacq X. Elife. 2022 Aug 17;11:e76870. doi: 10.7554/eLife.76870. PMID: 35976226

Surprising features of nuclear receptor interaction networks revealed by live-cell single-molecule imaging. Dahal L, Graham TGW, Dailey GM, Heckert A, Tjian R, Darzacq X. Elife. 2025 Jan 10;12:RP92979. doi: 10.7554/eLife.92979. PMID: 39792435

Bis(trifluoromethyl)carborhodamines: Highly Fluorogenic, Far-Red to Near-Infrared Dyes for Live Cell Fluorescence Microscopy, Activity-Based Sensing, and Single-Molecule Microscopy. Gerstner NC, McCann JT, Martin JG, Henn KM, Riske K, Anantakrishnan S, Graham TGW, Darzacq X, Miller EW. J Am Chem Soc. 2025 Jun 25;147(25):21950-21960. doi: 10.1021/jacs.5c05473. Epub 2025 Jun 11. PMID: 40501037

p300 is an obligate integrator of combinatorial transcription factor inputs. Ferrie JJ, Karr JP, Graham TGW, Dailey GM, Zhang G, Tjian R, Darzacq X. Mol Cell. 2024 Jan 18;84(2):234-243.e4. doi: 10.1016/j.molcel.2023.12.004. Epub 2023 Dec 29. PMID: 38159566

Automated live-cell single-molecule tracking in enteroid monolayers reveals transcription factor dynamics probing lineage-determining function. Walther N, Anantakrishnan S, Graham TGW, Dailey GM, Tjian R, Darzacq X. Cell Rep. 2024 Nov 26;43(11):114914. doi: 10.1016/j.celrep.2024.114914. Epub 2024 Oct 30. PMID: 39480809

Small-molecule disruption of androgen receptor-dependent chromatin clusters. Kohrt SE, Novak EJ, Tapadar S, Wu B, Strope J, Asante Y, Kim H, Chang MS, Gurdak D, Khalil A, Rood M, Raftery E, Stavreva D, Nguyen HM, Brown LG, Ramser M, Peer C, Meyers WM, Aboreden N, Chakravortee M, Sallari R, Nelson PS, Kelly KK, Graham TGW, Darzacq X, Figg WD, Oyelere AK, Corey E, Adelaiye-Ogala R, Gryder BE. Proc Natl Acad Sci U S A. 2024 Nov 26;121(48):e2406239121. doi: 10.1073/pnas.2406239121. Epub 2024 Nov 19. PMID: 39560645

Single-molecule tracking (SMT): a window into live-cell transcription biochemistry. Dahal L, Walther N, Tjian R, Darzacq X, Graham TGW. Biochem Soc Trans. 2023 Apr 26;51(2):557-569. doi: 10.1042/BST20221242. PMID: 36876879