The DeNardo Lab @WUSM

The DeNardo Lab @WUSM The DeNardo Lab @WUSM The DeNardo Lab @WUSM

The DeNardo Lab @WUSM

The DeNardo Lab @WUSM The DeNardo Lab @WUSM The DeNardo Lab @WUSM
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Tumor Microenvironment and Immunology Research: Keys To New Therapies

Tumor Microenvironment and Immunology Research: Keys To New TherapiesTumor Microenvironment and Immunology Research: Keys To New TherapiesTumor Microenvironment and Immunology Research: Keys To New Therapies

Tumor Microenvironment and Immunology Research: Keys To New Therapies

Tumor Microenvironment and Immunology Research: Keys To New TherapiesTumor Microenvironment and Immunology Research: Keys To New TherapiesTumor Microenvironment and Immunology Research: Keys To New Therapies

About Us

We aim to understand how immune responses shape and are shaped by tumor progression and anti-cancer therapy. We aim to exploit these weaknesses to improve patient outcomes by enhancing responses to conventional or immunotherapies.

Mentorship in the DeNardo Lab

The DeNardo Lab is dedicated to training the next generation of scientists and cancer researchers. As such, our group welcomes all individuals, regardless of physical ability, gender, sexual orientation, age, race/ethnicity, religion, or cultural background.

We are a team of scientists with diverse backgrounds and experiences, who have created a nurturing and inclusive environment that fosters a sense of belonging. United by a common goal—to fight cancer through research—we measure our success not only by the discoveries we make but also by the community we build to achieve them. Additionally, we take pride in the career and personal growth of each individual involved in our research as they progress through their training journey within our team.

Publications

See All Our Published Work

Highlighted Recent Published Research

Senescence Defines a Distinct Subset of Myofibroblasts That Orchestrates Immunosuppression in Pancreatic Cancer

Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy

Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy

Cancer Discovery 2024

Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy

Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy

Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy

Translation: See NCT05669482

Science Translational Medicine 2024

Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity

Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy

Stromal Reprogramming by FAK Inhibition Overcomes Radiation Resistance to Allow for Immune Priming and Response to Checkpoint Blockade

Translation: See WUSM SPORE

Cancer Cell 2023

Stromal Reprogramming by FAK Inhibition Overcomes Radiation Resistance to Allow for Immune Priming and Response to Checkpoint Blockade

Stromal Reprogramming by FAK Inhibition Overcomes Radiation Resistance to Allow for Immune Priming and Response to Checkpoint Blockade

Stromal Reprogramming by FAK Inhibition Overcomes Radiation Resistance to Allow for Immune Priming and Response to Checkpoint Blockade

Translation: See NCT04331041

Cancer Discovery 2023

Fibrosis induced by resident macrophages has divergent roles in pancreas inflammatory injury and PDAC

Stromal Reprogramming by FAK Inhibition Overcomes Radiation Resistance to Allow for Immune Priming and Response to Checkpoint Blockade

Tumor-associated fibrosis impairs immune surveillance and response to immune checkpoint blockade in non–small cell lung cancer

Nature Immunology 2023

Tumor-associated fibrosis impairs immune surveillance and response to immune checkpoint blockade in non–small cell lung cancer

Stromal Reprogramming by FAK Inhibition Overcomes Radiation Resistance to Allow for Immune Priming and Response to Checkpoint Blockade

Tumor-associated fibrosis impairs immune surveillance and response to immune checkpoint blockade in non–small cell lung cancer

Science Translational Medicine 2023

Our Research

Example Project: Dendritic Cells as Regulators of Tumor Immunity

Our lab focuses on understanding the impact of metastatic site-specific factors on immune responses in pancreatic ductal adenocarcinoma (PDAC). Our research has revealed that conventional dendritic cells (cDCs), essential for initiating anti-tumor immunity, exhibit significant dysfunction in both primary and metastatic PDAC, driven by site-specific differences in the tumor microenvironment (TME). Using state-of-the-art genomic, imaging, and functional analyses in human PDAC samples and mouse models, we aim to determine how metastatic sites influence immune priming, systemic immunity, and responses to therapy. By uncovering these mechanisms, our work seeks to improve immunotherapeutic strategies tailored to the unique immune landscapes of metastatic PDAC, ultimately enhancing patient outcomes.

Example Project: Fibroblast Heterogeneity (Senescence in the TME)

Our lab focuses on understanding how the tumor microenvironment (TME) shapes immune responses in pancreatic ductal adenocarcinoma (PDAC). Our recent findings highlight the role of senescent cancer-associated fibroblasts (SenCAFs) in promoting tumor progression by altering immune surveillance and extracellular matrix properties. Through cutting-edge biophysical and immunological techniques, we aim to determine how SenCAFs influence tumor immunity, myeloid cell function, and metastatic progression. Ultimately, our research seeks to uncover novel therapeutic strategies that target stromal senescence to enhance anti-tumor immunity and improve patient outcomes.

Example Project: Macrophage Heterogeneity

Our lab is focused on understanding the heterogeneity of macrophages in cancer, particularly how their diverse subtypes respond differently across various tissues and organs. This variability, driven by the tumor microenvironment, significantly impacts the effectiveness of immunotherapy, as macrophages can adopt pro-tumor or anti-tumor functions depending on their location. By leveraging innate immune agonists, we aim to reprogram cancer-associated macrophages to adopt anti-tumor roles, enhancing their ability to support immune responses against tumors. We are particularly interested in how organ-specific responses influence the reprogramming of these macrophages and their interaction with other immune cells. Ultimately, our research seeks to develop targeted strategies that use innate immune agonists to modulate macrophage function, improving cancer immunotherapy outcomes across different cancer types.

WUSM's SPORE in Pancreatic Cancer

Our translational research program possesses both breadth and depth. Our team has repeatedly demonstrated its ability to translate basic science discoveries to therapeutic approaches. Recent examples of this ability include advances in our understanding of the tumor micro-environment (TME) or tumor-mediated immune suppression, which have successfully moved from discovery to preclinical models and ultimately into clinical trials.. The Washington University SPORE in Pancreatic Cancer at Siteman Cancer Center includes patients with all disease stages, and its trials are led by many investigators from multiple disciplines. The clinical program is well established, and our growing reputation has facilitated academic and clinical partnerships, leading to numerous clinical trial opportunities. Since the SPORE’s inception, over 1,254 pancreatic cancer patients have been enrolled in a clinical trial. Thirty eight percent (476 patients) of these patients participated in one or more therapeutic trials).

The Pancreatic Cancer SPORE includes four research programs, an administrative core and two shared resource cores, and research opportunities for collaboration including developmental research and career enhancement programs. Clinical trials are an important and active part of the Pancreatic Cancer SPORE. The long-term goal of the Pancreatic Cancer SPORE is to improve PDAC patient survival. To achieve this goal, our SPORE will collaborate both within Washington University and with external institutions. Our investigators expect no singular approach to solve PDAC and fully commit to supporting young investigators and evaluating new ideas. Our SPORE will provide access to pancreatic cancer-specific resources to further this goal.

For any additional information about the Pancreatic Cancer SPORE, please contact David DeNardo at ddenardo@wustl.edu or Christina Kasting at c.pritchard@wustl.edu.

Involvement in Ongoing Clinical Trials

Immunologic Effects of CDX-301 and CDX-1140 in Resectable Pancreatic Cancer Patients

Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

Purpose: Evaluating Our Ability to Leverage Dendritic Cell-Targeted Therapy in Pancreatic Cancer Patients

NCT04536077

Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

Purpose: Evaluating Co-Targeting 

Tumor-Stroma Interactions to Improve Response to Radiation Therapy.

NCT04331041

Employing CD11b-Agonists to Render PDAC Responsive to Immunotherapy

Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

Employing CD11b-Agonists to Render PDAC Responsive to Immunotherapy

Purpose: To Evaluate Reprogramming Macrophages Through Integrins as a Novel Immunotherapy.

Coming Soon (See WUSM SPORE)

Meet the DeNar-Dawgs

Principal Investigator

David DeNardo, PhD

Graduate Students

Jessica Alexander

Jessica Alexander

Jessica Alexander

PhD Student

MCB Program

alexander.j.m @ wustl.edu

I study Kras and its interaction with the tumor microenviorment.  Outside of the lab I enjoy drawing and painting, listening to music, playing the trumpet, thrifting and antiquing, and trying new things! 

Jie Chen

Jessica Alexander

Jessica Alexander

PhD Student

MGG Program

chen.jie1 @ wustl.edu

I study how to harness radiation therapy (RT)-induced immunogenic cell death to treat PDAC. Outside of the lab, you’ll find me playing the piano, trying new restaurants, playing video and board games, and spending time with my cat. 

Alice Kao

Jessica Alexander

Blake Sells

PhD Student

MGG Program

akao @ wustl.edu

I study immune TMEs across primary and metastatic PDAC, particularly focusing on the macrophage population. Outside of the lab, I like running, hiking and spending time with my cat.

Blake Sells

Jessica Alexander

Blake Sells

MD/PhD Student

Cancer Biology Program

blake.sells @ wustl.edu

 I study how cancer-associated fibrosis and cancer-associated fibroblast phenotypes are modulated in the setting of immunotherapy and the resulting impact this remodeling has in the creation of an effective anti-tumor immune response. Outside of lab, I love to read, try new restaurants, and learn new sports.  

Dev Sen

Alyssa Weinstein

Maddie Turner

PhD Student

MCBProgram

d.sen @ wustl.edu

 I am studying how stromal senescence and metabolic changes influence anti-tumor immune responses and metastasis. Outside of the lab, I enjoy biking, listening to music, and experimenting with new recipes in the kitchen.

Maddie Turner

Alyssa Weinstein

Maddie Turner

MD/PhD Student

Cancer Biology Program

m.c.turner @ wustl.edu

 I am studying how to improve efficacy of radiation therapy in PDAC by combining radiation with other targeted therapies. In my free time I enjoy rock climbing, running in Forest Park, cooking/baking, playing board games, and going to concerts/live music!

Alyssa Weinstein

Alyssa Weinstein

Alyssa Weinstein

PhD Student

Cancer Biology Program

agweinstein @ wustl.edu

 I study dendritic cell differences at the primary and metastatic sites of PDAC. Outside of the lab, you will find me at the CrossFit gym, running around Forest Park, cooking or baking, hiking with my dog, or cuddling on the couch with my cat! 

Faculty & Staff

Brett Knolhoff

Liang-I Kang, MD, PhD

Liang-I Kang, MD, PhD

Lab Manager

bknolhoff @ wustl.edu

I am the lifeblood of this lab, managing the mouse colony as well as everyday operations large and small. Outside of the lab, I enjoy spending time with my wife and two kids. I am an avid sports fan, Go UK Wildcats! In my free time I enjoy playing golf with the guys.

Liang-I Kang, MD, PhD

Liang-I Kang, MD, PhD

Liang-I Kang, MD, PhD

Assistant Professor of Pathology & Immunology 

kangl @ wustl.edu

 I am a board-certified anatomic pathologist. In the DeNardo Lab, I am studying the tumor microenvironment of liver metastases in pancreaticcancer. Outside of lab, I enjoy collecting recipes, reading cookbooks and baking blogs/newsletters, and baking.  

Usman Panni, MD

Liang-I Kang, MD, PhD

Usman Panni, MD

Surgical Oncology Resident

usmanypanni @ wustl.edu

Utilizing novel immunotherapeutic strategies to modulate tumor microenvironment in lung cancer. 

Faiz Ahmad, PhD

Liang-I Kang, MD, PhD

Usman Panni, MD

Staff Scientist

afaiz @ wustl.edu

I conduct clinical biopsies for research, train scientists, design experiments, and analyze data across various projects and collaborations. Outside the lab, I’m passionate about music, books, and nature

Emily Butka, PhD

Emily Butka, PhD

Emily Butka, PhD

Bioinformaticist

ebutka @ wustl.edu

   I lead bioinformatics, data analysis and data management across trainees and projects. In my free time I serve as a bench scientist in my kitchen, trying and testing new and favorite recipes.

Olivia Dres

Emily Butka, PhD

Emily Butka, PhD

Research Technician

d.olivia @ wustl.edu

     To some, I am the mIHC expert; to others, I’m Olivia. I joined the DeNar-Dogs as an American Cancer Society DiCR Intern nearly three years ago and now work full-time. Currently, I work on a myriad of projects, helping others in lab, as well as independent projects. I am currently studying for th

Research Technician

d.olivia @ wustl.edu

     To some, I am the mIHC expert; to others, I’m Olivia. I joined the DeNar-Dogs as an American Cancer Society DiCR Intern nearly three years ago and now work full-time. Currently, I work on a myriad of projects, helping others in lab, as well as independent projects. I am currently studying for the MCAT, as I want to pursue an MD-PhD, but when I have free time, I enjoyed reading, backpacking, and traveling.

Claire Ku

Emily Butka, PhD

Sarah Baek

Undergraduate Student

Biology and Anthropology: Global Health and Environment

claireku @ wustl.edu

I am an undergraduate student at WashU and aspiring future physician. I joined the lab through the American Cancer Society DiCR Program and am currently studying immune profiles of the PDAC TME with my bench mentor, Maddie. In my spare time, I 

Undergraduate Student

Biology and Anthropology: Global Health and Environment

claireku @ wustl.edu

I am an undergraduate student at WashU and aspiring future physician. I joined the lab through the American Cancer Society DiCR Program and am currently studying immune profiles of the PDAC TME with my bench mentor, Maddie. In my spare time, I love to explore the outdoors, play the piano, and dance.

     

Sarah Baek

Emily Butka, PhD

Sarah Baek

Undergraduate Student

Biology and Psychological & Brain Sciences

baek.s.s @ wustl.edu

I'm a current undergraduate student at Washington University working part-time to support the gavage team. In my free time, I love drawing, playing the saxophone, and trying new video games.

Contact Us

Please reach out to collaborate or join our team!

The DeNardo Lab is affiliated with the Division of Molecular Oncology at Washington University in St. Louis School of Medicine. Prospective trainees are invited to email David DeNardo with their CV. @...ddenardo@wustl.edu

DeNardo Lab @ WUSM

660 S Euclid Ave, St. Louis, MO, USA

Copyright © 2025 DeNardo-Lab@WUSM - All Rights Reserved.

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