The Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of Ruth Bader Ginsburg, represents a joint effort to support the career advancement of a female scientist engaged in pancreatic cancer research. The Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of John Robert Lewis, represents a joint effort to encourage and support early career scientists engaged in pancreatic cancer research who are members of racial or ethnic groups that have been shown to be underrepresented in the cancer-related sciences workforce. 

2024 Grantees

Lustgarten Foundation-AACR Pancreatic Cancer Career Development Award, in Honor of John Robert Lewis

Research

There is an immediate need for more effective treatments for pancreatic cancer. Most pancreatic ductal adenocarcinoma (PDAC) cells rely heavily on the catabolic recycling process, autophagy. Targeting autophagy in vitro and in vivo has shown encouraging results leading to several clinical trials in PDAC. Despite some favorable responses, the impact on overall PDAC survival with these therapies is limited, likely due to inherent and acquired resistance. Recently, Dr. Towers found that cultured PDAC cells also acquire resistance to pharmacological autophagy inhibition. She proposes that a better understanding of these adaptive mechanisms will help identify ideal combination therapies to improve the efficacy of autophagy inhibition in pancreatic cancer patients. Preliminary analyses from Dr. Towers’ lab suggest that PDAC cells resistant to autophagy inhibition have an increased dependency on nucleotide metabolism pathways. Dr. Towers’ project will leverage these mechanisms to identify new combination therapies to treat pancreatic cancer.

Biography

Dr. Towers completed both her doctorate and postdoctoral studies at the University of Colorado. During this time, she developed unique CRISPR/Cas9 tools to understand the recycling process, autophagy, in cancer cells. Dr. Towers is currently an assistant professor at the Salk Institute of Biological Studies in San Diego, where she launched her own lab in 2021 that focuses on targeting autophagy in pancreatic cancer. She was recently named a Pew-Stewart Scholar and V scholar and has received the Black in Cancer Young Investigator Award, Chan Zuckerberg Initiative Diversity Leadership Award, and the NIH New Innovator Award. 

Acknowlegment of Support

“I am so grateful to The Lustgarten Foundation and AACR for funding our work. It’s an honor to be funded by this award in the name of the civil rights leader John Robert Lewis. This will help us make fundamental discoveries about pancreatic cancer metabolism and identify better combination therapies.”

Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of Ruth Bader Ginsburg

Research

Pancreatic cancer has a survival rate of less than 12% beyond 5 years post diagnosis. This highlights the urgent need for improved treatments as current therapies face significant patient resistance. Immunotherapy, while successful in certain cancers, has limited efficacy in pancreatic cancer due to a highly immunosuppressive tumor microenvironment characterized by extensive infiltration of tumor-associated neutrophils. The immunosuppressive function of tumor-associated neutrophils is dependent upon the increased production of reactive oxygen species, primarily by myeloperoxidase. Although myeloperoxidase inhibitors show promise in other diseases, their application in cancer remains unexplored. The proposed studies will provide mechanistic insight into how myeloperoxidase regulates tumor-associated neutrophil function and impacts immunotherapy response. This project aims to investigate whether inhibiting myeloperoxidase improves immune checkpoint therapy, which could be a clinically translatable treatment strategy that would expand current therapeutic options for pancreatic cancer patients.

Biography

Dr. Liu earned her bachelor’s degree from the University of British Columbia and her doctorate in medical biophysics from the University of Toronto. Following her doctoral studies, Dr. Liu completed her postdoctoral fellowship at the University of Texas MD Anderson Cancer Center. She is currently an assistant professor in the Department of Microbiology, Immunology and Cell Biology at West Virginia University.

Acknowledgment of Support

“I’m incredibly honored to receive the 2024 Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of Ruth Bader Ginsburg. Her legacy in advancing gender equality has paved the way for my career as a woman scientist. This award supports my pancreatic cancer research and boosts my confidence, affirming the potential impact of my work.”

2023 grantees

Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of Ruth Bader Ginsburg

Research

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed after distant metastases are present. Recent anatomical studies use 3D mapping approaches to study invasion patterns of localized pancreatic cancer; however, studies of 3D PDAC morphology at distant sites is lacking. Dr. Kiemen proposes to profile 3D anatomical, immune, and transcriptomic signatures of pancreatic cancer liver metastases and use this information to . She plans to use CODA (a technique for quantifying complex microanatomy) to three-dimensionally reconstruct liver tissue. She will then compare untreated and neoadjuvant chemotherapy- treated human liver, utilizing spatial transcriptomics to profile regions of interest. This project has the potential to improve understanding of PDAC invasion in the liver and to improve the ability to assess response to treatment.

Biography

Dr. Kiemen received her undergraduate degree in 2016 from the University of Michigan Ann Arbor, majoring in Chemical Engineering. She received her master’s degree in 2017 from the London School of Economics and Political Science, majoring in Philosophy. She received her doctorate in 2021 from the Johns Hopkins University, in the Department of Chemical & Biomolecular Engineering. She is currently an assistant professor of pathology and oncology at the Johns Hopkins University School of Medicine.

Acknowledgment of Support

“I am honored to be a recipient of a 2023 Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of Ruth Bader Ginsburg, for a proposal studying pancreatic cancer morphology in liver metastases using 3D mapping tools. It is an honor to receive this award in the name of such an iconic and inspiring figure in our society.”

Lustgarten Foundation-AACR Pancreatic Cancer Career Development Award, in Honor of John Robert Lewis

Research

Dr. Ferrer and her colleagues’ studies have recently shown that glutathione S-transferase, Gstt1, is required for dissemination and metastasis of pancreatic cancer and is retained within a latent subset of existing metastases. This subset is endowed with metastasis-initiating potential and preserves an expression signature characteristic of disseminated tumor cells associated with poor prognosis. An understanding of how this subset of cells remains latent while retaining metastasis-initiating capacity is still limited. Dr. Ferrer will investigate cell-intrinsic and microenvironmental mechanisms governing metastasis-initiating cells (MICs). Using a combination of orthotopic lineage-tracing models, gene expression profiling, and genetic approaches, she seeks to uncover insights into MIC ecosystems during each stage of the metastatic cascade and lay the foundation for the development of novel combination therapy regimens to target MICs in pancreatic cancer.

Biography

Dr. Ferrer made significant contributions to understanding how oncogenic alterations drive metabolic reprogramming in cancer during her doctoral work. She then continued her training as a postdoctoral fellow at Massachusetts General Hospital where she studied cancer metastasis in the context of identifying gene expression changes that are unique to existing metastatic tumors, particularly in pancreatic cancer. She is currently a faculty member of the Department of Pharmacology and the Greenbaum Comprehensive Cancer Center at the University of Maryland, Baltimore, where her lab focuses on identifying characteristics of MICs.

Acknowledgement of Support

“I am extremely honored to receive the 2023 Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research, in Honor of John R. Lewis. The award will allow my group to explore critical questions regarding how pancreatic cancer cells metastasize and survive, while also providing a supportive environment for underrepresented minority trainees.”

2022 grantees

Lustgarten Foundation-AACR Pancreatic Cancer Career Development Award, in Honor of John Robert Lewis

Research

The pro-tumorigenic activities of Heparan sulfate proteoglycans (HSPGs) are regulated by enzymatic modification of their heparan sulfate (HS) moieties. While mammalian heparanases promote extracellular matrix remodeling, invasion, and metastasis, bacterial heparinase depolymerizes HS through a contrasting mechanism, resulting in the suppression of tumor growth. However, the inability to restrict bacterial heparinase activity to tumor tissue has limited its use as a therapeutic agent. Using attenuated, tumor-targeting Salmonella typhimurium (ST) vectors, Dr. Manuel and his team have developed the first recombinant ST expressing functional heparinase through a tightly regulated, inducible promoter. The goal of their study is to determine the impact of this novel agent on nutrient scavenging and therapeutic resistance in models of pancreatic cancer.

Biography

Dr. Manuel earned his bachelor’s degree in Microbiology from San Diego State University and his PhD in Virology from Harvard. He is currently an Assistant Professor at the Beckman Research Institute of the City of Hope. The overall goal of his research program is to develop microbial-based therapies for the treatment of solid and hematological malignancies, i.e., “Bugs as Drugs”. His lab has been primarily focused on engineering recombinant, tumor-colonizing Salmonella to curtail processes contributing to therapeutic resistance in pancreatic cancer, namely desmoplasia and macropinocytosis.

Acknowledgment of Support

The Lustgarten Foundation-AACR Pancreatic Cancer Career Development Award, In Honor of John Robert Lewis, will allow me and my team to delve into key aspects of our microbialbased therapy. This is an important endorsement of our work and will ultimately have a significant impact on patients with advanced pancreatic cancer.

Lustgarten Foundation-AACR Pancreatic Cancer Career Development Award, in Honor of Ruth Bader Ginsburg

Research

Oncogenic KRAS (KRAS*) is the key driver of pancreatic ductal adenocarcinoma (PDAC) PDAC, maintaining tumor growth, and thereby, making it an ideal therapeutic target. However, both pre-clinical and clinical studies reveal adaptive resistance mechanisms in cancer to the treatment of KRAS* inhibitors (KRASi). Dr. Hou recently discovered that tumor-associated macrophages (TAMs) drive the KRAS* bypass by nourishing PDAC cells. In the project, Dr. Pingping Hou will explore the TAM subpopulation that promotes KRASi resistance in spontaneous PDAC mouse models and dissect the crosstalk of “pro-resistance” TAMs with tumor cells and cytotoxic T cells by various single-cell assays. The mechanistic insights gained can facilitate the development of novel combinatorial approaches with KRASi.

Biography

Dr. Hou received her PhD in cell biology from Peking University. After training in cancer biology as a postdoctoral fellow at the University of Texas MD Anderson Cancer Center, she joined the Center for Cell Signaling and the Department of Microbiology, Biochemistry and Molecular Genetics at Rutgers New Jersey Medical School. She is currently a tenure-track Assistant Professor at Rutgers New Jersey Medical School.

Acknowledgment of Support

With the support from the 2022 Lustgarten Foundation-AACR Pancreatic Cancer Career Development Award, In Honor of Ruth Bader Ginsburg, I am able to employ state-of-the-art single-cell technologies to comprehensively characterize the remodeling of tumor-associated macrophages and delineate the intercellular interactions that regulate pancreatic tumor response to KRAS inhibitors.