Kyle Cromer, PhD

Asst Professor in Residence
Research Description: 

While we have long known the location of disease-causing mutations in the genome, the discovery of CRISPR finally gave us the ability to correct these typos back to what they should be in healthy patients. 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.

Primary Thematic Area: 
Human Genetics
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
The research interest of my lab lies at the intersection of CRISPR-based genome editing and protein/cell engineering with special focus on hematopoietic stem cells and red blood cell disorders.


Featured Publications: 

Ultra-deep sequencing validates safety of CRISPR/Cas9 genome editing in human hematopoietic stem and progenitor cells.

Nature communications

Cromer MK, Barsan VV, Jaeger E, Wang M, Hampton JP, Chen F, Kennedy D, Xiao J, Khrebtukova I, Granat A, Truong T, Porteus MH

Gene replacement of α-globin with β-globin restores hemoglobin balance in β-thalassemia-derived hematopoietic stem and progenitor cells.

Nature medicine

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, Sheehan VA, Tisdale JF, Dever DP, Porteus MH

Improving the safety of human pluripotent stem cell therapies using genome-edited orthogonal safeguards.

Nature communications

Martin RM, Fowler JL, Cromer MK, Lesch BJ, Ponce E, Uchida N, Nishimura T, Porteus MH, Loh KM

Highly Efficient and Marker-free Genome Editing of Human Pluripotent Stem Cells by CRISPR-Cas9 RNP and AAV6 Donor-Mediated Homologous Recombination.

Cell stem cell

Martin RM, Ikeda K, Cromer MK, Uchida N, Nishimura T, Romano R, Tong AJ, Lemgart VT, Camarena J, Pavel-Dinu M, Sindhu C, Wiebking V, Vaidyanathan S, Dever DP, Bak RO, Laustsen A, Lesch BJ, Jakobsen MR, Sebastiano V, Nakauchi H, Porteus MH

Global Transcriptional Response to CRISPR/Cas9-AAV6-Based Genome Editing in CD34+ Hematopoietic Stem and Progenitor Cells.

Molecular therapy : the journal of the American Society of Gene Therapy

Cromer MK, Vaidyanathan S, Ryan DE, Curry B, Lucas AB, Camarena J, Kaushik M, Hay SR, Martin RM, Steinfeld I, Bak RO, Dever DP, Hendel A, Bruhn L, Porteus MH