Figure 1. Circos plots of somatic point mutations and copy number mutations identified in cutaneous T cell. lymphoma. Point mutations are indicated by black triangles; deletions, light blue boxes; amplifications, red boxes; translocations, royal blue lines; intrachromosomal rearrangements, green lines.
The Choi Lab
We are a technology-based laboratory that utilizes cutting-edge genomics, genome wide genetic screens, and mouse models to identify novel therapeutic strategies to cure cancer. These strategies are designed to target the immunogenicity, the genetics, and the epigenetics of skin cancer. The overarching goal of our lab is to utilize high-dimensional data to elucidate disease mechanisms with the goal of identifying novel therapies.
The Scientific Approach
We have three broad areas of interest.
1. Gene Discovery to Molecular Mechanisms: Cancer is fundamentally a genetic disease. Cancer cells acquire mutations in the cancer genome cause changes to transcription and lead to the altered expression of cancer-promoting proteins. We are utilizing Omics approaches to identify identify disease promoting mutations and utilizing human and animal models to show how these mutations contribute to disease. We have elucidated the genetic landscape of a number of cancers and related disorders. These genetic maps provide critical insights into disease origins, disease evolution, and responses to therapies.
In the process we have identified and functionally validated a number of oncogenes and tumor suppressors not previously identified in cancer including CD28 and RLTPR.
2. Computational Clinical Oncology. We are utilizing OMICS which include DNA, RNA, and Chromatin sequencing to elucidate the molecular features of patient samples. From these analyses we are identifying targetable molecular features that are shared across patients and features that are unique to each patient. A primary focus for us is to understand how cancers and individual patients respond or do not respond to immunotherapies.
For example, our work in Merkel cell carcinoma clearly delineated the rationale underlying immune checkpoint therapy for virus-negative cancers and has thus been cited over 50 times in the past year.
3. Development of Novel Tools. In the course of our studies, we have found that publicly available tools may be inadequate to answer the questions we are seeking. We are therefore developing novel technology based approaches. If you are interested, please feel free to ask us more about it.
We are an energetic team of scientists unified for our passion for curing cancer and having fun. Learn more about us here.
Our lab has tremendous momentum. Since the opening of the lab in September, 2015, we have authored or co-authored 19 manuscripts! Learn more about recent publications from the lab.
In addition, our lab has been fortunate to receive a number of awards. Joonhee was awarded the Translational Bridge Science Award! Alex has received a prestigious grant for his research in the lab. Jae has been fortunate to receive a number of prestigious grants and awards including the NIH New Innovator Award, the Damon Runyon Clinical Investigator, the Doris Duke Clinical Scientist, the ASCI Young Physician Scientist Award, and the AAD Young Investigator of the Year Award.
Figure 2. Identification of RLTPR (p.Q575E) as a novel putative oncogenic mutation in T cell cancers.
The team headlined by Dr. Joonhee Park has made dramatic improvements in our understanding of the genetic basis of cutaneous T cell lymphoma. By studying a larger cohort of 220 CTCLs, she has implicated 55 genes in CTCL pathogenesis, including 17 genes not previously implicated. Importantly, she has provided the first genetic and functional evidence that RLTPR is a T cell-specific oncogene. The mechanism is interesting and somewhat unexpected. Unlike other oncogenes, RLTPR has no known enzymatic domains. The p.Q575E alteration therefore appears to alter protein-protein interactions. p.Q575E enables preassembly of an important NF-kB signaling complex. In the presence of concomitant T cell receptor signaling agonists, this complex increases TCR signaling flux over 30 fold. We believe these findings will deepen our mechanistic understanding of CTCL and therefore enable the rational development of novel therapeutic strategies.
Read more about Joonhee’s work here.
Come join our fight against cancer! We are looking for motivated, energetic postdoctoral fellows, graduate students, and bioinformaticians to join the Choi lab. We are actively recruiting students because we know that they can bring a great deal of energy, intelligence, and enthusiasm for science and medicine.
If you are interested, please contact us:
Northwestern University Feinberg School of Medicine
303 East Superior St.
Chicago, IL 60611
“Cancer was not disorganized chromosomal chaos. It was organized chromosomal chaos.”
― Siddhartha Mukherjee,