‘ImmunoX’ Initiative a Radical Collaboration Across UCSF

Innovative Model to Drive Understanding of the Immune System in Health and Disease

By Nicholas Weiler

Kathy Lam works in the lab with Renuka Nayak
Kathy Lam (left) a postdoctoral fellow in the department of Microbiology & Immunology, works with Renuka Nayak, MD, PhD, assistant adjunct professor in Rheumatology. The new Bakar ImmunoX Initiative aims to break down the barriers that traditionally separate immunology research by disease area. Photo by Susan Merrell

UC San Francisco is launching the Bakar ImmunoX Initiative, an innovative research program that will promote collaborative, cutting-edge research and data sharing to catalyze discoveries about the central role of the immune system in human health and harness its power to treat a wide range of diseases.

Boosted by a significant new gift from the Gerson Bakar Foundation, ImmunoX aims to break down the barriers that traditionally separate immunology research by disease area, and instead organize the UCSF immunology community around a set of collaborative “CoProjects” that will tackle fundamental questions in the field.

Matthew “Max” Krummel, PhD

Matthew “Max” Krummel, PhD, is a UCSF professor of pathology and one of the leaders in developing ImmunoX. Photo by Maurice Ramirez

These CoProjects will be conducted within the UCSF CoLabs (previously referred to as Central Research Laboratories), an integrated research platform currently in development. The CoLabs are a pillar of the University’s reimagining of its original campus at Parnassus Heights as a next-generation hub for research, education and patient care. The CoLabs will provide scientists across the University with access to a shared ecosystem of state-of-the-art research facilities for processing clinical tissue samples; performing single-cell genomic, proteomic, and imaging experiments; and analyzing and curating the resulting data.

Using the UCSF CoLabs platform, ImmunoX will enable UCSF clinician-scientists, laboratory scientists, and data scientists to analyze the role of the immune system in diseases from cancer, where immunotherapies have already proven effective, to chronic viral infections or immune-mediated neurodegeneration. The resulting findings will also be made available to the broader UCSF community through a structured data library, enabling this unique and valuable data to be continuously mined by researchers and students with different questions and perspectives.

Bringing the immunology community at Parnassus Heights together to share resources and tackle ‘blue-sky’ projects in understanding human disease is the first glimpse of the bright future we envision for the entire Parnassus campus.

Chancellor Sam Hawgood, MBBS

ImmunoX is envisioned as an anchor program for the revitalized Parnassus Heights campus, building upon the strengths of UCSF’s Immunology Program, which is ranked first in the nation by US News and World Report.

“This is an extraordinary opportunity to harness UCSF’s strengths in immunology to drive new strategies for treating diseases,” said UCSF Chancellor Sam Hawgood, MBBS. “Bringing the immunology community at Parnassus Heights together to share resources and tackle ‘blue-sky’ projects in understanding human disease is the first glimpse of the bright future we envision for the entire Parnassus campus.”

Searching for Immune Patterns Across Human Disease

The initiative was inspired by a growing recognition that immune cells throughout the body use common tools and programs to respond to many different situations. These include deciding whether to fight off a viral infection or merely contain it when a full response could damage sensitive tissues, or recognizing which bacteria pose a threat and which are helpful and beneficial to the organism’s health.

“We are coming to understand the immune system as the adjudicator of all tissue, the peacemaker as well as the destroyer,” said Matthew “Max” Krummel, PhD, a UCSF professor of pathology and one of the leaders in developing ImmunoX.

This insight is epitomized by the early days of cancer immunotherapy, when Krummel and colleagues developed ipilimumab (Yervoy), based on the discovery that tumor cells often trick immune cells into leaving them alone by hijacking molecular “brakes” that are supposed to prevent the immune system from harming the body’s own tissues. Ipilimumab and later generations of immunotherapy have led to dramatic recoveries for many patients with melanoma and other cancers by deactivating these molecular brakes and allowing immune cells to resume their fight against tumors.

More recently, Krummel and others in the UCSF immunology community have realized that emerging technologies for monitoring and harnessing the immune system could have applications far beyond cancer. Adjusting dysfunctional or ineffective immune responses could be used for conditions ranging from chronic infectious diseases such as HIV/AIDS to immune-mediated diseases like allergies, asthma, and type 1 diabetes, and from inflammatory diseases of the bowel, liver, lung and brain to disorders of the microbiome, the resident microbial populations that normally provide benefits to the body.

We are coming to understand the immune system as the adjudicator of all tissue, the peacemaker as well as the destroyer.

Matthew “Max” Krummel, PhD

To pursue such immune-based therapies for a range of human diseases, Krummel developed the ImmunoX Initiative with colleagues Mark Anderson, MD, PhD, of the UCSF Diabetes Center; Mark Ansel, PhD, and Jason Cyster, PhD, of the Department of Microbiology and Immunology; Jeroen Roose, PhD, of the Department of Anatomy; and Qizhi Tang, PhD, of the Department of Surgery.

“Understanding the immune system’s varied roles in healthy and diseased tissues is a major goal of biomedical research and a key to developing the next generation of immunotherapies for cancer and beyond,” said Dan Lowenstein, MD, UCSF’s executive vice chancellor and provost. “We are excited that our immunology faculty are taking this bold step which is very much in keeping with UCSF as one of the world’s leaders in this field.”

In addition to the co-founders listed above, the ImmunoX leadership committee includes interim Bakar ImmunoX Chief Strategist Vincent Chan, PhD, and faculty members Anita Sil, MD, PhD, of the Department of Microbiology and Immunology; Adrian Erlebacher, PhD, of the Department of Laboratory Medicine; Tiffany Scharschmidt, MD, of the Department of Dermatology; Mark Looney, MD, and Susan Lynch, PhD, of the Department of Medicine.

Qizhi Tang (second from left), PhD, of the Department of Surgery, is one of the developers of ImmunoX. Photo by Barbara Ries

Initiative To Drive Collaborative Research and Data Sharing

The anchor gift from the Gerson Bakar Foundation will invest in the people, technologies, and research platforms needed to drive the ImmunoX vision of collaborative immunological research while also supporting a broader set of resources to promote collaborative research projects across the university.

The gift will initially support ImmunoX CoProjects focused on analyzing immune activity and identifying novel therapeutics in cancer, neurodegenerative diseases, and chronic viral infections. The Bakar gift will provide funds to jumpstart several CoLabs, including a new Disease to Biology CoLab to process tissue samples from clinical labs into their component cells; a Flow Cytometry CoLab to count, sort, and analyze the composition of these cells; a Genomics CoLab to perform single-cell analysis of gene activity and to develop innovative methods for analyzing and modifying gene function; a Biological Imaging Development CoLab for detailed microscopic analysis; and a new Data Sciences CoLab to develop bioinformatic frameworks for storing, analyzing, and sharing the data produced by the CoLabs pipeline.

ImmunoX also envisions creating an ImmunoX Data Library, a common repository for member research findings, enabling researchers and students across the university to mine the data to answer their own unique research questions.

“The entire UCSF biomedical community stands to benefit from this innovative model,” said Talmadge E. King Jr., MD, dean of the School of Medicine. “It will provide researchers and physician-scientists with greater access to samples and other resources, allow immunology faculty members to more easily collaborate to understand the role of the immune system across different disease states, and enhance the student experience through exposure to the vast possibilities of transforming healthcare through immunological research.”

The entire UCSF biomedical community stands to benefit from this innovative model.

Talmadge E. King Jr., MD

In addition, the Bakar gift will support postdoctoral researchers and clinical fellowships, and enable the recruitment of top new immunology faculty. It will also support a number of other initiatives designed to advance an engaged, collaborative, and diverse immunology community, including career development program for technicians, and a career/life balance initiative that will provide research support for graduate students and postdoctoral researchers for a full year during childbearing leave.

“UCSF is engaging in a bold experiment in scientific social engineering, with the hypothesis that the scientific community will learn more by collaboratively generating and sharing data to understand the role of the immune system across many different diseases that have traditionally been studied in isolation,” Krummel said. “We hope that ImmunoX can serve as a beacon to the rest of the world by proving that institutions can accelerate new discoveries by facilitating this kind of collaborative enterprise and encouraging researchers to break down the walls that have sequestered us in our own little labs.”

About UCSF CoLabs

The UCSF CoLabs are envisioned as an integrated research pipeline that can support UCSF’s biomedical research mission by providing a complementary set of research services, including tissue processing, single cell analysis of gene activity and protein expression, and biological imaging of cells’ appearance and behavior.

“Instead of individual faculty having to find collaborators on their own, who may be based at another campus on the other side of town, the idea is to build a coordinated pipeline of cutting-edge services and make them available to all faculty through a sustainable new funding model that will ensure the facilities are always equipped with the latest technology and staffed by expert technologists,” said Lindsey Criswell, MD, MPH, DSc, vice chancellor of research at UCSF, who is overseeing the development of the CoLabs with physician-scientist David Erle, MD, director of the UCSF Functional Genomics Core Facility.

ImmunoX support, coupled with support from UCSF leadership, has been absolutely essential for development of the CoLabs initiative,” said Erle. “Consistent with the collaborative spirit of ImmunoX, its leaders have been working closely with University leadership and dozens of UCSF faculty and staff since January 2018 to develop CoLabs as a resource for the entire UCSF research community. We look forward to involving an even larger share of the community, as CoLabs begins its first phase of operation later in the 2018-2019 academic year.”

UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises three top-ranked hospitals – UCSF Medical Center and UCSF Benioff Children’s Hospitals in San Francisco and Oakland – as well as Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff Children’s Physicians and the UCSF Faculty Practice. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. UCSF faculty also provide all physician care at the public Zuckerberg San Francisco General Hospital and Trauma Center, and the SF VA Medical Center. The UCSF Fresno Medical Education Program is a major branch of the University of California, San Francisco’s School of Medicine.