John A. Pulikkan, Ph.D.
Associate Investigator, Versiti Blood Research Institute
Assistant Professor, Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin
Dr. Pulikkan completed his Ph.D. in Human Biology from Ludwig Maximilian University of Munich, Germany under the supervision of Prof. Wolfgang Hiddemann and Prof. Gerhard Behre at the Helmholtz Zentrum Munich and Klinikum Grosshadern. His work elucidated the first direct mechanism by which C/EBPα regulates cell cycle control in hematopoiesis and provided strong evidence that restoration of microRNA levels could be a novel therapeutic avenue in cancer.
For his post-doctoral research, Dr. Pulikkan joined Prof. Lucio Castilla’s laboratory at the University of Massachusetts Medical School. He co-developed AI-10-49, a small molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC, which is associated with inv(16) leukemia. This work provided proof-of-principle that protein-protein interactions and oncogenic transcription factors, so-called “undruggable” targets in cancer therapy can be effectively targeted by small molecule inhibitors. In a follow-up study, Dr. Pulikkan showed that pharmacologic inhibition of the CBFβ-SMMHC/RUNX1 interaction by AI-10-49 leads to RUNX1-mediated changes in MYC enhancer chromatin dynamics, which in turn results in inhibition of the MYC transcriptional program and apoptosis. This study brought novel insights on how cancer driver mutations ‘hijack’ chromatin dynamics through deregulating the SWI/SNF chromatin remodeling complex/ Polycomb repressive complex (PRC) axis.
Dr. Pulikkan joined the Versiti Blood Research Institute in Milwaukee as an Associate Investigator in 2019. His team developed the first conditional genetic mouse model for CEBPA mutant AML and discovered chromatin regulation as the main pathway disrupted, opening avenues for novel treatment strategies. Additionally, Dr. Pulikkan’s team discovered how deregulated protein synthesis pathways, such as the N-MYC/eIF4G1 axis, contribute to the development and progression of inv(16) AML, identifying new therapeutic targets. By developing innovative models, including bone marrow organoids and genetic models, the Pulikkan lab is creating powerful platforms to study hematopoiesis and accelerate the discovery of next-generation therapies for blood cancers.
Dr. Pulikkan’s outstanding achievements have been recognized by many prestigious awards, including the American Society of Hematology (ASH) Scholar Award, American Cancer Society (ACS) Scholar Award, Alex's Lemonade Stand Foundation Young Investigator Award, and Lauri Strauss Leukemia Foundation Discovery Grant.