^Oncology

Kim E. Nichols Lab

Unraveling the impact of genetic variants on the development of cancer and hyperinflammation

About the Nichols Lab

Germline genetic variants can increase the risk for cancer and certain immune disorders. Our laboratory is interested in identifying what those variants are and how they contribute to disease. We focus on understanding how specific germline genetic changes impact blood cell development and function. This work will allow us to explore new diagnostic and treatment approaches for pediatric patient populations.

The Team

The Nichols Lab has a vibrant and interactive team committed to increasing knowledge of disease mechanisms and developing novel therapies for children at increased risk for cancer and hyperinflammation.

Meet the Team

In the news

Learn about how scientists at St. Jude have shown that a drug that inhibits two major inflammatory signaling proteins works better than drugs inhibiting either protein alone in models of hemophagocytic lymphohistiocytosis (HLH).

In the news

St. Jude scientists found that early screening means early detection of new cancers for pediatric patients with an underlying genetic predisposition at their most treatable stages. Learn more.

In the news

DNA isn't destiny, but genetic predispositions do underlie many cancers. St. Jude scientists have gained a nuanced understanding of cancer predisposition and are learning more to help personalize patient therapies. Learn more. #StJudeOn

Our research summary

At the heart of our laboratory’s research program is the aim to better understand how germline genetic variants can lead to cancer and particular hyperinflammatory disorders. Armed with this more in-depth knowledge, our work will inform more effective treatments for children who are at a greater risk for developing cancer and hyperinflammation.

Cancer predisposition: discovery efforts

Broadly speaking, our research focuses on defining the prevalence and spectrum of germline genetic variants that predispose to childhood cancer and understanding how these variants impact clinical presentation, tumor biology, treatment response and overall outcome. We use a variety of complementary approaches to mine the genomes of cancer prone kindreds and large cohorts of children with cancer. Through this work, we aim to gain a better understanding of the underlying disease mechanisms and then use this information to improve the diagnosis and management of children and families at increased genetic risk for cancer.

Analysis of ETV6-mediated predisposition in childhood ALL

Through the efforts described above, we identified that germline variants in ETV6, the gene encoding an essential hematopoietic transcription factor, are associated with predisposition to thrombocytopenia and B-acute lymphoblastic leukemia (B-ALL). We are currently working to better understand how germline variants in ETV6 impact the transcriptional landscape of hematopoietic stem and progenitor cells and B lymphoid progenitors to promote leukemia formation. We have generated experimental mouse models and iPSC systems with targeted mutations to interrogate the function and impact of several identified ETV6 variants. With this knowledge, we aim to better understand the role of ETV6 in B-leukemogenesis and to use this information to develop novel approaches to treat or even prevent ETV6-related leukemia.

Pathogenesis of hyperinflammation

Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal hyperinflammatory syndrome characterized by the dysregulated activation of cytotoxic T cells and macrophages which secrete high levels of pro-inflammatory cytokines. Our laboratory uses patient samples and animal models to decipher the cellular and molecular mechanisms underlying development of HLH. The “cytokine storm” associated with HLH is also found in other hyperinflammatory scenarios as with COVID-19 and response to CAR T-cell therapy. Using HLH as a model disease will inform treatment of cytokine storm syndromes more broadly, St. Jude is now leading a multi-institution clinical trial for HLH based on research conducted in our laboratory.