Kyle Cromer, PhD
Assistant Professor
Surgery
School of Medicine

While this effort has yielded novel therapies in the clinic, in my own lab I want to look beyond simply correcting DNA typos and instead use genome editing to introduce novel functions into cells for therapeutic purposes. Examples include: -Engineering red blood cells to deliver novel protein payloads -Creating genome editing strategies that bias stem cell differentiation to produce clinically relevant cell types -Engineering kill switches to prevent differentiation into unwanted cell types -Developing novel ways to regulate therapeutic protein stability and expression using small molecules -Multiplexing editing in order to introduce multiple genome editing events simultaneously (such as correcting a disease-causing mutation and adding a kill switch that could be activated in the case of an adverse event)

With special focus on hematopoietic stem cells and red blood cells, my main goal is to close the gap between synthetic biologists and clinicians in order to address current bottlenecks in treating the hemoglobinopathies and other blood disorders. While this is my current focus, the tools I am developing are cell type- and disease-agnostic and I am always open to expanding these concepts into new areas.

• Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease.
  Science translational medicine 2021 Lattanzi A, Camarena J, Lahiri P, Segal H, Srifa W, Vakulskas CA, Frock RL, Kenrick J, Lee C, Talbott N, Skowronski J, Cromer MK, Charlesworth CT, Bak RO, Mantri S, Bao G, DiGiusto D, Tisdale J, …
• Gene replacement of α-globin with β-globin restores hemoglobin balance in β-thalassemia-derived hematopoietic stem and progenitor cells.
  Nature medicine 2021 Cromer MK, Camarena J, Martin RM, Lesch BJ, Vakulskas CA, Bode NM, Kurgan G, Collingwood MA, Rettig GR, Behlke MA, Lemgart VT, Zhang Y, Goyal A, Zhao F, Ponce E, Srifa W, Bak RO, Uchida N, Majeti R, …
• Improved Genome Editing through Inhibition of FANCM and Members of the BTR Dissolvase Complex.
  Molecular therapy : the journal of the American Society of Gene Therapy 2020 de Alencastro G, Puzzo F, Pavel-Dinu M, Zhang F, Pillay S, Majzoub K, Tiffany M, Jang H, Sheikali A, Cromer MK, Meetei R, Carette JE, Porteus MH, Pekrun K, Kay MA
• Identification of preexisting adaptive immunity to Cas9 proteins in humans.
  Nature medicine 2019 Charlesworth CT, Deshpande PS, Dever DP, Camarena J, Lemgart VT, Cromer MK, Vakulskas CA, Collingwood MA, Zhang L, Bode NM, Behlke MA, Dejene B, Cieniewicz B, Romano R, Lesch BJ, Gomez-Ospina N, …
• Priming Human Repopulating Hematopoietic Stem and Progenitor Cells for Cas9/sgRNA Gene Targeting.
  Molecular therapy. Nucleic acids 2018 Charlesworth CT, Camarena J, Cromer MK, Vaidyanathan S, Bak RO, Carte JM, Potter J, Dever DP, Porteus MH
• Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas.
  Proceedings of the National Academy of Sciences of the United States of America 2015 Cromer MK, Choi M, Nelson-Williams C, Fonseca AL, Kunstman JW, Korah RM, Overton JD, Mane S, Kenney B, Malchoff CD, Stalberg P, Akerström G, Westin G, Hellman P, Carling T, Björklund P, Lifton RP
• Identification of somatic mutations in parathyroid tumors using whole-exome sequencing.
  The Journal of clinical endocrinology and metabolism 2012 Cromer MK, Starker LF, Choi M, Udelsman R, Nelson-Williams C, Lifton RP, Carling T