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Mullighan Lab: About Us

Welcome to the lab of Charles G. Mullighan, MBBS (Hons), MSc, MD

Front row (L to R): Chunxu Qu, Hiroki Yoshihara (former), Debbie Payne-Turner, Kathryn Roberts, Ilaria Iacobucci, Michelle Churchman (former), Ian Moore, Ashley Hill and Zhaohui Gu. Back row (L to R): Yunchao Chang, Evan Comeaux (former), Yaqi Zhao, Charles Mullighan, Aman Seth, Kirsten Dickerson, Elena Varotto, Bryan Huber and Dave Cervi.

The goal of the Mullighan laboratory is to identify the constellations of inherited and acquired genetic alterations that drive the development of acute lymphoblastic leukemia and related disorders, and translate these discoveries into mechanistic insights and advances in diagnosis and therapy. The lab has a strong track record of performing state-of-the art integrated genomic analysis of thousands of ALL samples coupled with detailed mechanistic analysis, and has made many of the seminal discoveries that have transformed our understanding of the genetic basis of ALL, and the way in which the disease is now diagnosed and treated. Highlights include:

• Identifying alterations disrupting lymphoid development in B-ALL (Nature 2007)
• IKZF1 alterations as a central determinant of high risk B-ALL (Nature 2008, NEJM 2009, Cancer Cell 2015)
• Identification and characterization of Ph-like ALL (Cancer Cell 2012 and 2016, NEJM 2014, JCO 2017)
• Identification of the majority of the known germline mutations that predispose to ALL (PAX5, Nat Genet 2013; TP53 Nat Genet 2013; IKZF1 Cancer Cell 2018)
• The genetics of clonal evolution and relapse (Science 2008, Nature 2011 and 2017, Nat Commun 2015)
• Identification of new subtypes of B-ALL (e.g. MEF2D, Nat Commun 2015 and DUX4/ERG deregulated ALL, Nat Genet 2016)
• Defining the genomic basis of lineage ambiguous, stem cell leukemias (early T cell precursor leukemia, Nature 2012; mixed phenotype acute leukemia, Nature 2018)

In addition to studying an unparalleled genomic dataset from human samples, the lab uses a broad range of experimental approaches including biochemical approaches, generation of engineered mouse models using recombineering and CRISPR/Cas9 genome editing, RNAi and CRISPR functional genomic screens, epigenomic and chromatin profiling, single cell genomics, xenograft propagation, cross-species genomics and preclinical studies. The lab is very interested in looking “outside” the leukemic cell to understand treatment failure, for example, by modeling the role of genotype dependent and independent interactions with the bone marrow microenvironment as a mechanism of resistance, and examining the genomic determinants of responsiveness to immunotherapy.

The laboratory is closely integrated with the St. Jude Comprehensive Cancer Center Hematological Malignancies Program and many of the discoveries from the laboratory have been incorporated into clinical trials at St. Jude and worldwide. We have strong links with pediatric and adult cooperative groups including the Children’s Oncology Group, the NCT TARGET initiative, MD Anderson Cancer Center, The ACRIN Eastern Cooperative Oncology Group, and the Alliance Cancer and Leukemia Group B.

Research is supported by multiple sources, including an NCI Outstanding Investigator Award, Leukemia and Lymphoma Society SCOR and TRP grants, and foundation grants.

The laboratory provides an exceptional environment for training in experimental and computational biology relevant to acute leukemia, and prospective postdoctoral fellows with experience and/or interest in joining the laboratory are strongly encouraged to contact Dr. Mullighan. Funded training positions are available, and the majority of trainees have secured competitive training fellowships, publications in leading journals, and positions as scientists or independent faculty.