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 (Pulikkan et al., Blood 2009; Pulikkan et al., Blood 2010; Pulikkan et al., Leukemia 2010).

 

For his post-doctoral research, Dr. Pulikkan joined Prof. Lucio Castilla’s laboratory at the University of Massachusetts Medical School. He co-discovered AI-10-49, a small molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC, which is associated with inv(16) leukemia (Illendula* and Pulikkan* et al., Science 2015; Pulikkan et al., Blood 2012). 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. Currently, AI-10-49 is under development as an anti-leukemic drug. 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 (Pulikkan et al., Cell 2018). 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’s outstanding achievements during his post-doctoral research have been recognized by many prestigious awards, including the American Society of Hematology (ASH) Scholar Award, Alex's Lemonade Stand Foundation Young Investigator Award, Lauri Strauss Leukemia Foundation Discovery Grant and UMASS Cancer Center researcher award. During his doctoral research Dr. Pulikkan was awarded the German José Carreras Leukemia Foundation Research Fellowship, Wilhelm Roux Research Scholarship and Daimler Benz Foundation Research Fellowship.

 

Dr. Pulikkan joined Versiti Blood Research Institute, Milwaukee in 2018 as an Associate Investigator. His lab's research focuses on deciphering the interplay between transcription factors and chromatin dynamics in normal and malignant hematopoietic stem cells, and understanding the function of non-coding RNAs in myeloid development and leukemia. The long-term goal of the Pulikkan lab is to identify and characterize novel therapeutic targets, and translate them to the clinic for leukemia treatment.

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