Lung Cancer

Current Projects
Saket Rahul Bagde, PhD

Most cancers develop in the epithelial tissue, which includes the skin and internal organ linings.  Hemidesmosomes (HDs) are adhesive structures that anchor epithelial cells to the underlying base layer and maintain tissue integrity. While HD disassembly occurs normally during wound healing, tumor cells can exploit this process to detach and spread to other parts of the body. Dr. Bagde is studying how HD components interlock like Lego blocks to form stable HDs in healthy tissues and how they disassemble in cancerous tissues. To investigate this phenomenon, Dr. Bagde plans to develop organoids—self-organizing mini-organs grown in a petri dish to study disease progression. By creating simple base layers that simulate the supportive properties of the native organ base layer, he plans to promote the growth of both normal and cancerous organoids. This work has the potential to support the development of personalized cancer therapies based on patient-derived tumor samples. Dr. Bagde received his PhD from Cornell University, Ithaca and his MS and BS from the Indian Institute of Science Education and Research, Pune.

Project title: "Integrin a6ß4 in hemidesmosome dynamics: structural and functional insights for tissue homeostasis, organoid growth, and cancer"
Institution: Boston Children's Hospital
Award Program: Fellow
Sponsor(s) / Mentor(s): Timothy A. Springer, PhD
Cancer Type: Head and Neck Cancer, Breast, Colorectal, Lung
Research Area: Aging
Debadrita Bhattacharya, PhD

Intra-tumoral heterogeneity (ITH), or the evolution of distinct cell types within a tumor, underlies most fatal features of cancer and presents a great therapeutic challenge. Using small cell lung cancer (SCLC), a highly heterogeneous and lethal form of lung cancer, as a model, Dr. Bhattacharya [Robert Black Fellow] will study how ITH arises during cancer progression. She will employ emerging genomics techniques to characterize the cellular subtypes that comprise SCLC tumors and identify “druggable” transcription factors which, if targeted, could reduce tumor heterogeneity in this cancer. By profiling thousands of cells from treatment-naïve and therapy-resistant tumors, Dr. Bhattacharya aims to identify the “master-regulators” of the cellular subtypes that expand upon treatment in SCLC. She will then evaluate the role of these factors in human patient-derived cell lines, with the goal of uncovering novel mechanisms underlying ITH in human cancers. Dr. Bhattacharya received her PhD from Cornell University and her BS from the University of Calcutta.

Project title: "Investigating molecular and cellular mechanisms of intra-tumoral heterogeneity in small-cell lung cancer"
Institution: Stanford University
Named Award: Robert Black Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Julien Sage, PhD
Cancer Type: Lung
Research Area: Epigenetics
Laura Crowley, PhD

Fibroblasts are one of the earliest known cell types and they contribute to many of the most burdensome lung diseases, including cancers, fibrosis, and emphysema; however, they are surprisingly poorly understood. Dr. Crowley [HHMI Fellow] will examine the different types of fibroblasts in the mouse lung to determine where they come from and how they function normally, as well as how they change with injury and disease. This will establish an important baseline for how these cells function in mice and also provide critical, long-term insights into how these cells may function in humans, where lung diseases are very difficult to treat and are among the leading causes of mortality worldwide. Though her work will directly analyze the fibroblasts and microenvironment around lung tumors, her findings could translate to many other solid tumor contexts. Dr. Crowley received her PhD from Columbia University, New York and her BA from Colby College, Waterville.

Project title: "Identifying fibroblast stem cells in organ maintenance, repair, and cancer"
Institution: Stanford University
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Mark A. Krasnow, MD, PhD
Cancer Type: Lung
Research Area: Stem Cell Biology
Rodrigo Gier, PhD

Drug therapies that selectively target proteins that drive the growth of tumor cells are rapidly becoming the standard of care for many cancers. However, tumors are often able to evade inhibition by targeted anti-cancer drugs by activating other proteins, leading to drug resistance. Dr. Gier [HHMI Fellow] is developing a new therapeutic approach that repurposes existing drugs to release highly toxic cargoes, known as payloads, that aggregate in drug-resistant cancer cells and kill them. As a general platform, it is applicable to a wide range of solid and liquid cancers. Dr. Gier received his PhD from University of Pennsylvania, Philadelphia and his BA from Swarthmore College, Swarthmore. 

Project title: "Targeted chemical aggregation as a general strategy to overcome cancer drug resistance"
Institution: University of California, San Francisco
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Kevan M. Shokat, PhD
Cancer Type: Blood, Other Cancer, Lung
Research Area: Chemical Biology
Alex M. Jaeger, PhD

Recent advances in genomic and proteomic technologies have ushered in a new era of antigen-specific immunotherapies, including cancer vaccines. Such therapies depend upon immune system recognition and processing of antigens-proteins or fragments of proteins displayed on the cancer cell surface. However, our understanding of the principles that govern antigen presentation across cell types throughout the tumor microenvironment (TME) remains limited. Dr. Jaeger's [William Raveis Charitable Fund Innovator] research uses sophisticated mouse models to understand how cells present and process antigens in healthy lung tissue and the lung cancer TME. These studies will advance our understanding of how different patterns of antigen presentation activate different T cell pathways and identify opportunities to engineer next-generation immunotherapies. The fundamental insights gained from these studies will be broadly applicable to multiple cancer types.

Project title: "Engineering approaches to exploit MHC-II antigen presentation in cancer"
Institution: H. Lee Moffitt Cancer Center
Named Award: William Raveis Charitable Fund Innovator
Award Program: Innovator
Cancer Type: Lung
Research Area: Tumor Immunology
Tadashi Manabe, MD, PhD

Lung cancer remains the leading cause of cancer mortality. Substantial breakthrough discoveries, including the identification of lung cancer-specific genetic drivers (e.g., EGFR mutations, EML4-ALK fusion genes) and the development of molecular inhibitors of these pathogenic factors, have improved outcomes for patients with advanced-stage lung cancer. However, lung cancer cells eventually acquire resistance to these molecular inhibitors, resulting in progressive disease. Dr. Manabe’s [Connie and Bob Lurie Fellow] research focuses on protein compounds formed by the self-assembly of oncogenic fusion proteins such as EML4-ALK. These compounds initiate a signaling pathway that causes abnormal cell proliferation in cancer. Dr. Manabe will explore the newly discovered structures of signaling proteins with the goal of developing molecular therapies that enhance precision medicine strategies and improve the control of lung cancer. Dr. Manabe received both his MD and PhD from Keio University School of Medicine.

Project title: "Characterization of oncogenic kinase signaling by membraneless cytoplasmic protein granules"
Institution: University of California, San Francisco
Named Award: Connie and Bob Lurie Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Trever G. Bivona, MD, PhD
Cancer Type: Lung
Research Area: Signal Transduction
Manuel Osorio Valeriano, PhD

Human cells compact their vast genomes into the small confines of the nucleus by wrapping their DNA into a highly complex structure called chromatin. Packaging DNA into chromatin, however, affects all nucleic acid-transacting machines (e.g., transcription factors) that need to access the genomic information stored in the DNA. NuRD is a large multi-subunit protein complex that plays a major role in making chromatin either accessible or inaccessible. Dysregulation of NuRD and aberrant targeting of the complex can result in the emergence of several types of cancers, including breast, liver, lung, blood, and prostate cancers. Dr. Osorio Valeriano’s [Philip O'Bryan Montgomery, Jr., MD, Fellow] work will reveal mechanistic aspects of NuRD-mediated chromatin regulation and pave the way for the development of novel therapeutic approaches that target cancers more effectively. Dr. Osorio Valeriano received his PhD from Philipps University and his MSc and BSc from the National Autonomous University of Mexico.

Project title: "Molecular and structural basis of gene expression regulation by the nucleosome remodeling and deacetylase (NuRD) complex in human cancer"
Institution: Harvard Medical School
Named Award: Philip O’Bryan Montgomery Jr. MD Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Lucas Farnung, PhD, and Danesh Moazed, PhD
Cancer Type: Blood, Gastric, Breast, Lung, Prostate
Research Area: Structural Biology
Shreoshi Sengupta, PhD

Studies have shown that lung tumors are sustained through the formation of new blood vessels from pre-existing ones in a process called angiogenesis. Moreover, tumor cells secrete signaling proteins that help them communicate with each other and evade immune detection. However, most of these studies have been on late-stage lung tumors; our understanding of cell-cell interactions in the tumor environment during lung cancer initiation and early stages remains poor. Dr. Sengupta [Deborah J. Coleman Fellow] plans to identify the gene expression patterns in tumor cells, endothelial cells (blood-vessel-forming cells), and immune cells over time to understand how they engage in this cellular crosstalk, promoting tumorigenesis. She also plans to examine cell-cell interactions in early-stage lung cancer using organoids, or artificially grown miniature organs. This line of investigation will help understand the mechanisms underlying tumor initiation and lead to novel biomarkers that can help detect lung cancers earlier. The findings will also help identify novel therapeutic targets that can be inhibited to improve patient responses and survival. Dr. Sengupta received her PhD from Indian Institute of Science, Bangalore and her MS and BS from University of Calcutta, Kolkata.

Project title: "Decoding cell-cell interactions aiding angiogenesis and immune evasion in early-stage lung cancer"
Institution: Boston Children's Hospital
Named Award: Deborah J. Coleman Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Carla F. Kim, PhD
Cancer Type: Lung
Research Area: Cancer Genetics
Fyza Y. Shaikh, MD, PhD

Immunotherapy has significantly changed how lung cancer and melanoma are treated. Unfortunately, only a small percentage of patients experience long-lasting responses. Gut bacteria have emerged as a potential predictor of how patients will respond to immunotherapy and may even be adjusted to enhance the effect of immunotherapy. Dr. Shaikh aims to identify features of the gut microbiome that correlate with immunotherapy responses. She will focus on both individual bacteria as they change over the course of treatment and the metabolites made by the entire bacterial community in the colon. The goal of this project, since gut bacteria can be modified, is to develop microbiome-based treatments to be used in combination with immunotherapy to improve response rates or overcome immunotherapy resistance for patients.

Project title: "Defining microbiome stability and longitudinal shifts as biomarkers of tumor response to immune checkpoint inhibitors across multiple malignancies"
Institution: The Johns Hopkins University School of Medicine
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Cynthia L. Sears, MD, and Drew M. Pardoll, MD, PhD
Cancer Type: Lung, Skin
Research Area: Immunotherapy
David M. Walter, PhD

Dr. Walter focuses on splicing factor genes, which carry out the RNA splicing process and are widely mutated in lung cancer. The splicing factor U2AF1 is mutated in 2% of lung cancer patients, but 80% of these mutations are identical, making it one of the most common missense mutations in lung cancer. Scientists do not have a good understanding of why this mutation occurs, or how it promotes cancer development. Dr. Walter will use a combination of cell and mouse model systems along with patient data to identify the unique molecular and genetic features of U2AF1-mutant cancer cells with the goal of identifying new therapeutic targets for lung cancer patients.

Project title: "Identifying the selective mechanism behind U2AF1 mutations in lung adenocarcinoma"
Institution: Dana-Farber Cancer Institute
Award Program: Fellow
Sponsor(s) / Mentor(s): Matthew L. Meyerson, MD, PhD
Cancer Type: Lung
Research Area: Cancer Genetics
  • You can support our innovative researchers.