Grant Development Seed Awardees

2021

Regulation of PRMT1 by Amino Acids and CDK5

Dr. Wenjian Gan 

Primary Investigator: Wenjian Gan, Ph.D.

Post-translational modifications (PTMs), such as ubiquitination, phosphorylation and methylation, play a key role in maintaining signaling pathways in response to diverse environmental inputs. Aberrancies in key enzymes of these modifications may cause imbalanced signal transduction, contributing to human diseases including cancers. My lab is particularly interested in investigating the regulation and biological functions of protein arginine methyltransferases (PRMTs) in breast cancer and hepatocellular carcinoma progression.

Notably, PRMT1 is the main type I enzyme responsible for about 80% of arginine methylation. Previous studies showed that PRMT1 is upregulated in various cancers including breast cancer and hepatocellular carcinoma. This proposal will identify the upstream stimulus/regulator of PRMT1, providing a novel regulatory mechanism of PRMT1 biological function and a potential strategy targeting PRMT1 for cancer therapy.

A Novel Technology to Perform scRNA-Seq From Cryopreserved Human Tumors

Photo of Dr. Spyropoulos

Primary Investigator: Demetri Spyropoulos, Ph.D.

Collaborators: David Neskey, M.D., John Baatz, Ph.D., Martin Romeo, Ph.D., Denis Guttridge, Ph.D.

Tumors are often complex in nature, containing some cell types that are sensitive and some that are resistant to different therapies. Most cancers that relapse after treatment involve therapy-resistant subpopulations of such tumor cells. In order to know how to treat cancers so patients remain in long-term remission and don’t relapse, we need to understand the complexity of tumors.

New technologies now exist to determine tumor complexity, but they are very expensive and require immediate tumor processing before we can decide on which tumors to investigate. The research grant investigates a method for preserving and banking tumors live and intact for extended periods of time, so that informed decisions can be made on which sets of tumors to fully study and thereby develop the best therapeutic strategies.

Remodeling ER Morphology to Improve Tumor Immunotherapy

Dr. Thaxton

Primary Investigator: Jessica Thaxton, Ph.D.

Collaborator: Alex Andrews, Ph.D.

The tumor microenvironment (TME) presents extreme metabolic stress to tumor infiltrating lymphocytes (TILs) that debilitates their ability to control tumor growth. The endoplasmic reticulum (ER) is the central organelle through which cells experience stress. Our lab has shown that essential processes in the ER become dysregulated in the TME.

Our previous research led us to question whether the dynamic morphology of the ER becomes distorted in T cells in solid tumors. Our preliminary data indicate that ER morphology is compromised in CD8 TILs and that ER structure defines the capacity of T cells to control tumor growth.

This proposal will generate gene deletion tools in human T cells and a unique mouse model to study the role of ER shaping proteins to control T cell antitumor fate. New therapeutics that target ER architecture in TILs may extend across tumor types and to other dysmorphic tumor immune subsets, offering a panacea to reset immune homeostasis in tumors.