Adaptive Immunity Archives - Sanford Burnham Prebys

Eric has a broad background in chemical biology, with specific training and expertise in kinase inhibitors and targeted protein degradation, an emerging modality in which small molecules recruit E3 ligase complexes to target proteins to induce their ubiquitination and subsequent proteasomal degradation. He also has experience in pharmacological modulation of immune cells to improve anti-tumor immunity.

He received his PhD from the University of California San Francisco and postdoctoral training at the Dana-Farber Cancer Institute.

Education and Training

2021: Postdoctoral Fellow, Dana-Farber Cancer Institute / Harvard Medical School
2009: PhD, University of California San Francisco, 2015 BS, Duke University

Fellowship

Damon Runyon Cancer Research Foundation Fellowship

Related Disease
Cancer, Immune Disorders, Molecular Biology

Phenomena or Processes
Adaptive Immunity, Cancer Biology, Cell Biology, Disease Therapies, Tumor Microenvironment

Techniques and Technologies
Chemical Biology, Drug Discovery

Dysregulation of transcriptional circuits is a common hallmark of disease, and in particular is found in both tumor and host immune cells in cancer. Eric’s lab is focusing on developing and using chemical tools to modulate the activity of key transcriptional regulators of both tumor cells and host immune cells, with a long-term goal of identifying new therapeutic approaches.

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Showing 3 of 3

CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation.

Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, Chhabra S, Huang W, Liu H, Aref AR, Ivanova E, Paweletz CP, Bowden M, Zhou CW, Herter-Sprie GS, Sorrentino JA, Bisi JE, Lizotte PH, Merlino AA, Quinn MM, Bufe LE, Yang A, Zhang Y, Zhang H, Gao P, Chen T, Cavanaugh ME, Rode AJ, Haines E, Roberts PJ, Strum JC, Richards WG, Lorch JH, Parangi S, Gunda V, Boland GM, Bueno R, Palakurthi S, Freeman GJ, Ritz J, Haining WN, Sharpless NE, Arthanari H, Shapiro GI, Barbie DA, Gray NS, Wong KK

Cancer Discov 2018 Feb ;8(2):216-233

Bruton tyrosine kinase degradation as a therapeutic strategy for cancer.

Dobrovolsky D, Wang ES, Morrow S, Leahy C, Faust T, Nowak RP, Donovan KA, Yang G, Li Z, Fischer ES, Treon SP, Weinstock DM, Gray NS

Blood 2019 Feb 28 ;133(9):952-961

Acute pharmacological degradation of Helios destabilizes regulatory T cells.

Wang ES, Verano AL, Nowak RP, Yuan JC, Donovan KA, Eleuteri NA, Yue H, Ngo KH, Lizotte PH, Gokhale PC, Gray NS, Fischer ES

Nat Chem Biol 2021 Jun ;17(6):711-717

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“Cancer is one the main causes of death in the US. Our research is focused on understanding how we can harness the power of our immune system to attack and kill cancer cells and cure patients. I chose to join Sanford Burnham Prebys because of their collaborative research culture and state-of-the- art core facilities. I believe that teamwork is the foundation of scientific breakthroughs, and the Institute provides a perfect supportive and friendly environment to achieve this.”

Originally from the Netherlands, Kelly received her BS and MS from Utrecht University, and performed her PhD studies at the Netherlands Cancer Institute in Amsterdam working with Prof. Karin de Visser studying the role of the immune system in the metastatic spread of breast cancer. For her postdoctoral training, Kelly joined the lab of Prof. Max Krummel at the University of California San Francisco to study how tumor-associated myeloid cells affect anti-tumor T cell responses. Kelly is currently setting up her independent research team at Sanford Burnham Prebys.

Education

2016-2023: Postdoctoral Training, University of California San Francisco (Mentor: Prof. Max Krummel, focus on immune evasive cancer)
2017: PhD, Netherlands Cancer Institute Amsterdam/ Leiden University (Mentor: Prof. Karin de Visser, focus on role immune system in breast cancer metastasis, 2011-2016)
2011: MS, Biomedical Sciences, Utrecht University, Netherlands
2008: BS, Biology, Utrecht University, Netherlands

Honors and Recognition

2022: Selected Attendee for SITC Women in Cancer Immunotherapy Network (WIN) Leadership Institute
2022: Selected Attendee for Arthur and Sandra Irving Cancer Immunology Symposium
2022: Ray Owen Poster Award for Outstanding Poster Presentation at 60th Midwinter Conference for Immunologists at Asilomar (sponsored by AAI)
2020-2022: Parker Scholar Award awarded by the Parker Institute for Cancer Immunotherapy (PICI)
2018: Honorable Mention of poster presentation at UCSF/UCB/UCM Immunology Retreat
2018: Poster presentation ‘Excellence in Research Award’ awarded by the National Philanthropic Trust
2017-2019: NWO Rubicon postdoctoral fellowship awarded by the Netherlands Organization for Scientific Research (NWO)
2015: Best presentation award at the annual Tumor Cell Biology meeting of the Dutch Cancer Society (KWF)
2014: Travel scholarship awarded by the Dutch Foundation for Pharmacological Sciences (NSFW)
2010: Master scholarship awarded by the Dutch Cancer Society (KWF)

Memberships

2022-present: Society for Immunotherapy of Cancer (SITC)
2020-present: Parker Institute for Cancer Immunotherapy (PICI)
2012-present: American Association for Cancer Research (AACR)

Related Disease
Breast Cancer, Cancer Biology, Immune Disorders, Inflammation, Innate Immunity, Metastasis, Skin Cancer and Melanoma, Tumor Microenvironment, Tumorigenesis

Phenomena or Processes
Adaptive Immunity, Innate Immunity

Research Models
Mouse, Primary Cells

Techniques and Technologies
Cellular and Molecular Imaging

The Kersten lab studies the interactions between the immune system and cancer

We are fascinated by the crosstalk between the immune system and cancer. Our goal is to understand how cancer cells hijack the normal physiology and function of immune cells to support tumor growth and evade destruction by the immune system.

Kelly Kersten’s Research Report

Cancer immunotherapy, harnessing a patient’s immune system to fight cancer, has revolutionized the way we treat cancer. However, a large proportion of patients do not respond to this type of therapy, and we do not fully understand why. In the Kersten lab, we study how different immune cells affect anti-tumor immunity with the ultimate goal to improve therapies to fight cancer. Research in our lab is focused on understanding how interactions between different immune cells in the tumor microenvironment, specifically macrophages and T cells, affect anti-tumor immunity and responsiveness to immunotherapy. Why do T cells become dysfunctional and exhausted? How do exhausted T cells modulate the composition of immune cells in tumors? And how do macrophages shut down anti-tumor T cells? Our research aims to define the molecular mechanisms that regulate these reciprocal signals to design novel anti-cancer therapies. How immune cells function is highly context-dependent. Upon infiltration in the tumor microenvironment, immune cells face extremely harsh conditions characterized by nutrient deprivation, hypoxia and metabolic challenges resulting in their failure to function properly. We study how different environmental factors impact immune cell phenotype and function, with the goal to optimize their cancer-killing properties.

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Showing 3 of 3

Uptake of tumor-derived microparticles induces metabolic reprogramming of macrophages in the early metastatic lung.

Kersten K, You R, Liang S, Tharp KM, Pollack J, Weaver VM, Krummel MF, Headley MB

Cell Rep 2023 Jun 27 ;42(6):112582

Spatiotemporal co-dependency between macrophages and exhausted CD8(+) T cells in cancer.

Kersten K, Hu KH, Combes AJ, Samad B, Harwin T, Ray A, Rao AA, Cai E, Marchuk K, Artichoker J, Courau T, Shi Q, Belk J, Satpathy AT, Krummel MF

Cancer Cell 2022 Jun 13 ;40(6):624-638.e9

Understanding the tumor immune microenvironment (TIME) for effective therapy.

Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, Coussens LM, Gabrilovich DI, Ostrand-Rosenberg S, Hedrick CC, Vonderheide RH, Pittet MJ, Jain RK, Zou W, Howcroft TK, Woodhouse EC, Weinberg RA, Krummel MF

Nat Med 2018 May ;24(5):541-550

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Dr. Bradley received her doctorate from the University of California Berkeley, in 1981 in studies of CD4 T cell subsets that regulate humoral immune responses. Her work on the regulation of CD4 T cells continued during her postdoctoral training at The Oregon Primate Research Center and at the University of California, San Diego where she was appointed Assistant Research Professor in 1991. It was at this time she developed NIH sponsored her research program on CD4 T cells and discovered the key associations between migration and function. She joined The Scripps Research institute as an Assistant Professor in 1996 where she expanded her work on CD4 T cells into the arena of autoimmunity and discovered the essential role of the cytokine, interleukin-7, in the regulation of CD4 cell homeostasis.

She joined the Sidney Kimmel Cancer Center in 2001 as an Associate Professor, and was promoted to Professor in 2005. She joined Sanford Burnham Prebys as a Professor in the Infectious and Inflammatory Diseases Center in 2009. Dr. Bradley is recognized as a key contributor in the field of CD4 T cell biology, is an invited speaker at many national and international meetings, and serves on several study sections for the NIH as well as the Welcome Trust, Medical Research Council, and the JDRF.

Related Disease
Cancer, Infectious Diseases, Skin Cancer and Melanoma

Phenomena or Processes
Adaptive Immunity, Cell Signaling, Infectious Disease Processes, Inflammation

Anatomical Systems and Sites
Immune System and Inflammation

The research program in the Bradley Lab is focused on understanding the regulation of T lymphocytes in virus infections where the immune response results in viral clearance and the development of immunologic memory, and in chronic virus infections where the ongoing immune response leads to viral persistence and immune dysregulation. We are guided by these studies to interrogate cellular mechanisms that can be modulated to promote better responses not only to virus infections, but also to relieve immune inhibition in the setting of cancer where T cells progressively lose function. Understanding adhesion mechanisms underlie the ability of T cells to become localized in tissues to eradicate infections and tumors is a key underpinning of our work.

Our current focus is on two molecules that can function on T cells to initiate the processes that lead to their migration from the blood into tissue, CD44 and PSGL-1 (P-selectin glycoprotein-1). We have found that both of these receptors have key regulatory functions that are independent of their roles in migration. These proteins regulate the magnitude of T cell responses, as well as the survival and memory formation by T cells by different mechanisms, affecting processes in the T cell and stromal cell compartments.

Our ongoing studies of these immune checkpoint regulators using in vivo models indicate that they are promising therapeutic targets to enhance T cell responses to infections and cancer as well as to inhibit T cell responses in autoimmunity. We are therefore pursuing translational studies with the UCSD Moores Cancer center to analyze their regulation in human T cells in an effort to enhance patient responses to their tumors using in vivo modeling. In addition working to develop biologics for treatment of patients with autoimmunity and cancer.

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Showing 3 of 3

Striking a Balance-Cellular and Molecular Drivers of Memory T Cell Development and Responses to Chronic Stimulation.

Hope JL, Stairiker CJ, Bae EA, Otero DC, Bradley LM

Front Immunol 2019 ;10():1595

PSGL-1: A New Player in the Immune Checkpoint Landscape.

Tinoco R, Otero DC, Takahashi AA, Bradley LM

Trends Immunol 2017 May ;38(5):323-335

PSGL-1 Is an Immune Checkpoint Regulator that Promotes T Cell Exhaustion.

Tinoco R, Carrette F, Barraza ML, Otero DC, Magaña J, Bosenberg MW, Swain SL, Bradley LM

Immunity 2016 May 17 ;44(5):1190-203

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Dr. Blaho began her research career focused on how bioactive lipids contribute to the innate immune response against bacterial infection, characterizing roles for eicosanoids in the generation and resolution of Lyme arthritis pathology. The wild diversity of lipid species led Dr. Blaho to Weill Cornell Medical College in New York City to pursue postdoctoral training in the field of sphingolipids, particularly sphingosine 1-phosphate (S1P), and its receptors. Advancing to Instructor at Weill Cornell and later, Research Assistant Professor at Sanford Burnham Prebys, Dr. Blaho continued her research in lipid chaperones and receptor signaling, with an emphasis on cell-type differential effects on hematopoiesis and immunity in response to cell stressors. In August of 2019, Dr. Blaho joined the faculty at the Institute as an Assistant Professor in the Immunity and Pathogenesis program.

Why do you do what you do?

The immune system has the power to protect us from invading pathogens and cancer or to initiate a “self-destruct” sequence that consumes us with inflammation and autoimmunity. It is fascinating to me that a simple ubiquitous fat molecule like S1P can control the birth and destiny of immune cells.

Education

2014-2016: Instructor, Weill Cornell Medicine, Pathology and Laboratory Medicine and Neuroscience
2009-2014: Post-doctoral training, Weill Cornell Medicine, Pathology and Laboratory Medicine
2007-2009: Post-doctoral training, University of Missouri, Columbia, Veterinary Pathobiology
2007: PhD, University of Missouri, Columbia, Molecular Microbiology and Immunology – BS

Funding Awards and Collaborative Grants

National Heart, Lung, and Blood Institute R01
American Heart Association Scientist Development Grant
2014-15: Leon Levy Neuroscience Foundation Grant
2015: Foundation LeDucq SphingoNet Young Investigator Grant
2009-12: National Cancer Institute Individual Ruth L. Kirschstein Post-doctoral Fellowship

Honors and Recognition

2017: British Journal of Pharmacology Lecture: FASEB Summer Research Conference on Lysophospholipids and Related Mediators – from bench to clinic.
2014: Leon Levy Foundation Neuroscience Fellow
2010: Keystone Scholarship, Bioactive Lipids: Biochemistry and Diseases
2008: Keystone Scholarship, Eicosanoids and Other Mediators of Chronic Inflammation
2007: Young Investigator Award in Inflammation, Eicosanoid Research Foundation
2004: National Academy of Sciences Christine Mirzayan Policy Fellow, Institute of Medicine Board on Health Sciences Policy

Related Disease
Biochemistry, Immune Disorders, Inflammatory/Autoimmune Disease, Leukemia/Lymphoma, Molecular Biology, Multiple Sclerosis

Phenomena or Processes
Adaptive Immunity, Apoptosis and Cell Death, Cell Signaling, G-Protein Coupled Receptors, Hematopoiesis, Inflammation, Innate Immunity

Anatomical Systems and Sites
Hematopoietic System, Immune System and Inflammation, Vasculature

Research Models
Human Adult/Somatic Stem Cells, Mouse, Mouse Somatic Stem Cells, Primary Cells

Techniques and Technologies
Cell Biology, Cellular and Molecular Imaging, Confocal Microscopy, Fluorescence Microscopy, Gene Expression, Lipid Bilayers, Mass Spectrometry

The lipid sphingosine 1 phosphate (S1P) is found in high levels in the blood and lymph and is primarily carried by the protein ApoM, found on HDL. S1P can affect the cardiovascular, nervous, and immune systems via interaction with cell surface-expressed receptors, S1P1-5. My work is determining how changing S1P carrier or receptor expression and signaling can affect cells of the immune system, particularly in the bone marrow, and how this alters their ability to respond to stress or infection.

Select Publications

Showing 3 of 3

HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation.

Blaho VA, Galvani S, Engelbrecht E, Liu C, Swendeman SL, Kono M, Proia RL, Steinman L, Han MH, Hla T

Nature 2015 Jul 16 ;523(7560):342-6

HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation.

Galvani S, Sanson M, Blaho VA, Swendeman SL, Obinata H, Conger H, Dahlbäck B, Kono M, Proia RL, Smith JD, Hla T

Sci Signal 2015 Aug 11 ;8(389):ra79

An update on the biology of sphingosine 1-phosphate receptors.

Blaho VA, Hla T

J Lipid Res 2014 Aug ;55(8):1596-608

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Phenomena or Process: Adaptive Immunity

Education and Training

Fellowship

Select Publications

CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation.

Bruton tyrosine kinase degradation as a therapeutic strategy for cancer.

Acute pharmacological degradation of Helios destabilizes regulatory T cells.

Education

Honors and Recognition

Memberships

The Kersten lab studies the interactions between the immune system and cancer

Kelly Kersten’s Research Report

Uptake of tumor-derived microparticles induces metabolic reprogramming of macrophages in the early metastatic lung.

Spatiotemporal co-dependency between macrophages and exhausted CD8(+) T cells in cancer.

Understanding the tumor immune microenvironment (TIME) for effective therapy.

Striking a Balance-Cellular and Molecular Drivers of Memory T Cell Development and Responses to Chronic Stimulation.

PSGL-1: A New Player in the Immune Checkpoint Landscape.

PSGL-1 Is an Immune Checkpoint Regulator that Promotes T Cell Exhaustion.

Why do you do what you do?

Education

Funding Awards and Collaborative Grants

Honors and Recognition

HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation.

HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation.

An update on the biology of sphingosine 1-phosphate receptors.

Biography

Education and Training

Fellowship

Research

Select Publications

CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation.

Bruton tyrosine kinase degradation as a therapeutic strategy for cancer.

Acute pharmacological degradation of Helios destabilizes regulatory T cells.

Biography

Education

Honors and Recognition

Memberships

Research

Select Publications

Uptake of tumor-derived microparticles induces metabolic reprogramming of macrophages in the early metastatic lung.

Spatiotemporal co-dependency between macrophages and exhausted CD8(+) T cells in cancer.

Understanding the tumor immune microenvironment (TIME) for effective therapy.

Biography

Research

Select Publications

Striking a Balance-Cellular and Molecular Drivers of Memory T Cell Development and Responses to Chronic Stimulation.

PSGL-1: A New Player in the Immune Checkpoint Landscape.

PSGL-1 Is an Immune Checkpoint Regulator that Promotes T Cell Exhaustion.

Biography

Why do you do what you do?

Education

Funding Awards and Collaborative Grants

Honors and Recognition

Research

Select Publications

HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation.

HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation.

An update on the biology of sphingosine 1-phosphate receptors.