Before joining Ludwig Oxford in 2020, I was Professor of Cell Biology and C. H. Waddington Professor of Pediatrics at Harvard Medical School. I received my PhD from New York University and postdoctoral training at Princeton University. I joined Harvard Medical School as an Assistant Professor in 1991 and was appointed a Professor of Pathology in 2004. In 2009 I joined the Newborn Medicine Division of Boston Children’s Hospital.
I am interested in identifying key epigenetic regulators in cancer, elucidating their mechanism of action and providing the conceptual basis for translating our basic findings to the clinic via the development of new therapeutic strategies. With the discovery of the first histone methyl eraser, LSD1, in 2004, our group demonstrated that histone methylation is dynamically regulated, which overturned the long-held dogma that such modifications were static and irreversible. We have also discovered many additional histone demethylases with different specificities, and novel readers, including those that specifically recognise unmodified lysine and arginine and suggest that the unmodified states are not simply a ground neutral state of epigenetic information but rather likely code for epigenetic information as modified states.
We are also studying RNA modifications and how they impact gene expression regulation. In many ways this exciting field parallels the early days of chromatin biochemistry and biology, i.e., the nature and the biological and pathological functions of RNA modifications, as well as the enzymes responsible for writing, erasing and reading them, are just beginning to be understood.
At Ludwig Oxford, my lab is focusing on two cancers – acute myeloid leukaemia and diffuse intrinsic pontine glioma - where chromatin/epigenetics have been shown to play a crucial role in the maintenance of a poorly differentiated state. We are exploring combinatorial mechanisms that promote cancer cell differentiation and therefore may provide the rationale needed for therapeutic considerations. We are also exploring epigenetic regulators in cancer and the host immune system to find ways to turn “cold’ tumours “hot” and to help ensure sustained response to tumour immune checkpoint blockade therapy.
LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade
Sheng W. et al, (2018), Cell, 174, 549 - 563.e19
Re-programing Chromatin with a Bifunctional LSD1/HDAC Inhibitor Induces Therapeutic Differentiation in DIPG
Anastas JN. et al, (2019), Cancer Cell, 36, 528 - 544.e10
Nucleotide resolution profiling of m3C RNA modification by HAC-seq
Cui J. et al, (2020), Nucleic Acids Research
meCLICK-Seq, a Substrate-Hijacking and RNA Degradation Strategy for the Study of RNA Methylation.
Mikutis S. et al, (2020), ACS central science, 6, 2196 - 2208