Download Formation of a Strategic Partnership in Cancer Research between

White Paper for India-UChicago Cancer Workshop:
Formation of a Strategic Partnership in Cancer Research between
India and the University of Chicago
Sponsored by the University of Chicago Delhi Center and the National Institute of Biomedical Genomics (India)
on March 23 and 24, 2015
Organizers:
Marsha R. Rosner
Ben May Department for Cancer Research
University of Chicago Comprehensive Cancer Research Center
University of Chicago
[email protected]
Partha P. Majumder
National Institute of Biomedical Genomics
Kalyani, India
[email protected]
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1. Background:
The aim of this workshop, organized by Professor Marsha Rosner of the University of Chicago and Professor
Partha Majumder, National Institute of Biomedical Genomics (NIBMG), India, was to initiate a conversation
between researchers at the University of Chicago and at various Indian institutions geared towards
undertaking joint research and capacity-building initiatives on cancer biology. Our ultimate goal is to leverage
our respective strengths in the areas of genomics, signal transduction, big data analysis, and targeted
therapies to undertake novel research that will not only have immediate application to cancer diagnosis,
prognosis and therapeutic treatment, but will also serve as a model for addressing other diseases.
2. Attendees:
University of Chicago Delhi Centre: Professor Gary Tubb, Director
Department of Biotechnology, Govt. of India: Professor K. VijayRaghavan, Secretary; Dr. T.S. Rao, Senior
Adviser; Mr. S. Sinha, Adviser; Dr. Bindu Dey, Adviser.
University of Chicago: There were 6 participants from the University of Chicago: Professor Eileen Dolan,
Chair of the Committee on Phamacogenetics; Professor Geoffrey Greene, Chair of the Ben May Department for
Cancer Research and co-Director, Ludwig Center for Metastasis; Professor Melody Swartz, Director of the
Center for Immunobioengineering in the Institute for Molecular Engineering; Professor Kevin White, Director
of the Institute for Genomics and Systems Biology, Professor Everett E. Vokes, John E. Ultmann Professor of
Medicine and Radiation Oncology, Physician-in-Chief, University of Chicago Medicine and Biological Sciences
and Chair, Department of Medicine, and Professor Marsha Rosner, former Chair of the Ben May Department
for Cancer Research and founder of the Committee on Cancer Biology.
India: Dr. Mammen Chandy, Tata Medical Centre, Kolkata; Dr. Shubhada Chiplunkar, Advanced Centre
for Treatment, Research and Education in Cancer, Mumbai; Dr. Kartiki Desai, National Institute of Biomedical
Genomics, Kalyani; Professor Paturu Kondaiah, Indian Institute of Science, Bangalore; Dr. Sudhir Krishna,
National Centre for Biological Sciences, Bangalore; Professor Tapas Kundu, Jawaharlal Nehru Centre for
Advanced Scientific Research, Bangalore; Dr. Arindam Maitra, National Institute of Biomedical Genomics,
Kalyani; Professor Partha Majumder, National Institute of Biomedical Genomics, Kalyani; Dr. Mohandas
Mallath, Tata Medical Centre, Kolkata; Dr. Geetashree Mukherjee, Tata Medical Centre, Kolkata; Professor
Binay Panda, Genomics Applications and Informatics Technology Laboratories, Bangalore; Dr. Radhakrishna
Pillai, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram; Dr. Susanta Roychoudhury, Indian Institute
of Chemical Biology, Kolkata; Dr. Rajiv Sarin, Advanced Centre for Treatment, Research and Education in
Cancer, Mumbai; Professor Sharmila Sengupta, National Institute of Biomedical Genomics, Kalyani; Professor
Subrata Sinha, National Brain Research Centre, Manesar; Professor Kumar Somasundaram, Indian Institute of
Science, Bangalore; Professor Parul Chakrabarti, Sir J.C.Bose Trust, Kolkata
3. Where We Stand
Professor Gary Tubb and Professor K. VijayRaghavan welcomed this joint effort. Both affirmed their
commitment to building relationships between the University of Chicago and Indian institutions engaged in
cancer research. Professor VijayRaghavan stated that India has done well as a member of the International
Cancer Genome Consortium (ICGC) and stated that the initial findings of the ICGC, not only from the Indian
efforts but also from the efforts of other members, may be taken forward by embarking on in-depth research.
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He also stated that the Department of Biotechnology has a major commitment to cancer biology as
additionally exemplified by the series of Provocative Questions workshops recently conducted in India by DBT,
jointly with the National Cancer Institute in the United States. Both he and Professor Tubb strongly supported
the workshop and added that they would support similar workshops in the future, as well.
Here we list possible projects and collaborators from among the UChicago and India attendees but recognize
that the specific projects and collaborators may change and expand.
Cancer Type
There were two cancers that clearly were the foci of the majority of investigators attending the conference.
Most of the attendees from India were focused on either breast or head and neck cancer, two of the most
prevalent cancers in India, each of which served as the focus of a working group at the workshop. In addition,
there is active research in India focused on cervical and brain cancer.
Research Area
Two forefront and complementary approaches to cancer analysis and treatment were central themes at the
workshop: Medical genomics and Cancer immunotherapy.
What is the opportunity?
With the decreasing cost and increasing ease and speed of genomic sequencing, new drugs that target
individual patients’ tumors are being identified for more personalized treatments. However, these new drugs
have had disappointing impact in overall survival rates because most tumors mutate as the tumor progresses
and evolves. Thus, no matter how effective a drug might be at killing most of the tumor cells, there will always
exist some tumor cells that become resistant to the drug, only to later form new tumors with different
properties. Treatment with a new drug can lead to a vicious cycle of patient relapse, each time resulting in
more potent tumor cells and eventual mortality.
Immunotherapy is an exciting new avenue to treat cancer. It works by harnessing the patient’s own
immune system to attack tumor cells. Immunotherapy holds huge promise in treating millions of patients
whose cancers do not respond to current drug treatments. The past decade has seen remarkable growth in
molecular and cellular immunotherapy to capitalize on this promise - from incredible research advances to
innovative clinical application. Reflective of this excitement, cancer immunotherapy was named the 2013
“Breakthrough of the Year” by the leading scientific journal Science.
While immunotherapy works well for a subset of patients with certain cancers such as melanoma,
multiple challenges need to be overcome before it can realize its full potential. Immunotherapy depends on
both activating and recruiting host immune cells to kill the tumor, but tumors can evolve to evade these in a
variety of ways. Therefore, new approaches are desperately needed before the immense potential of cancer
immunotherapy can be realized clinically.
We propose that, by combining genomics-based targeted drug approaches with immunotherapy, we
can overcome the limitations of each strategy alone. For example, certain drugs kill tumor cells in a way that
stimulates the immune system. When these patients are also exposed to therapies that require an active
immune system, then the drugs and the immunotherapy can act cooperatively to eliminate cancer in patients.
With a focus on the immune system, it is possible to harness our evolving ability to design targeted drug
therapy with activation of immune cells that specifically target cancer cells.
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However, major challenges remain in translating these promising approaches to a larger variety of
cancer types, including those that are most difficult to treat with chemotherapy, such as triple-negative breast
cancer. In addition to tumor heterogeneity, there are multiple mechanisms of drug and immune-resistance
that arise to further promote tumor progression that we still do not completely understand. We have a long
way to go in realizing the full potential of targeted drug treatment combined with cancer immunotherapy.
One major issue that restricts progress is the limited communication and collaboration between
different research fields that contribute to cancer research – particularly those that arose from very different
disciplines, such as tumor immunology, nanotechnology, computational genomics, imaging and tissue
engineering. Here, we turn this model upside-down and propose a novel and innovative training program that
will have broad and long-term impact by developing science teams to facilitate interdisciplinary training.
Students from different fields, and in different countries, will work together towards a common goal, with the
benefits of having more than one faculty mentor to shape their perspectives and enrich their experiences. The
goals will be problem-based, while progress and integration will be facilitated by weekly videoconferenced
team meetings and semi-annual retreats in alternating locations.
4. Why University of Chicago and India?
The University of Chicago has a culture of innovation that is complemented by the focus on innovation in India
(exemplified by the new genomics institute NIBMG) as a top priority of the next ten years. To date, India has
lacked formal programs for research training of clinicians and has emphasized computational and engineering
careers over those in the clinical science research. The University of Chicago has strong training programs and
mentors in the biological and clinical sciences and unique computational resources including cloud-based
cancer databases as well as new, highly innovative and world-class molecular engineering programs. By
combining our respective strengths in biotechnology, computation and data analysis, as well as human
resources, we have an unprecedented opportunity to establish an ongoing collaboration through
interdisciplinary teams and make significant progress in this challenging disease.
5. What is the Opportunity?
Harnessing our relative expertise to create novel approaches for genomics and cancer Immunotherapy
We now have a unique opportunity to build teams between UChicago and India (coordinated by NIBMG) that
bridge clinical oncology with cutting-edge research labs in genomics, cancer biology and immunology,
immunoengineering and systems biology, focused on creating novel approaches to drug treatment and
immunotherapy. Specifically, we will develop an innovative, interdisciplinary team-based research program
focused on developing novel and integrative solutions to problems in cancer treatment. This research
program will center around the interdependent goals of (1) providing interdisciplinary training to pre- or postdoctoral cancer researchers across India and at UChicago, and (2) building international teams that bridge
different fields to address global challenges in cancer research and translation through innovative and
collaborative approaches.
We will seed this effort by forming interdisciplinary and international teams of researchers between at
least two laboratories with complementary expertise, one at UChicago and one at NIBMG or another Indian
university/institute. These teams will initially focus on oral or breast cancers — two major cancers in both the
US and India — and the genomic and immunological approaches that show promise to affect change in each.
In addition, we will bring strength in computational/ statistical science to analyze the "big data" emerging
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from these studies, and bioengineering to design novel strategies to address any hurdles to creating effective
immunotherapies.
Training
Our initial goal is to support two pre- or post-doctoral trainees in Indian laboratories and two trainees in
UChicago laboratories for each research project. In order to nurture expertise across teams, we will support
the joint fellowship program by building out a suite of virtual and in-person opportunities for cross-training
and mentorship, including:
 Workshops in India, jointly conducted by UChicago and NIBMG, which will focus on cancer biology,
cancer immunotherapy, and new technologies for cancer research. These workshops will be open to
senior PhD students and junior faculty members from institutions across India and will serve as the
basis for selection for exchange visits at UChicago.
 Exchange visits will include opportunities for trainees from India to participate in short- and long-term
research opportunities at UChicago; and for faculty/trainees from UChicago to train at an institution in
India (primarily those with a focus on genomics/computational biology).
 Skype and other video conferencing tools, including classes and seminars transmitted across UChicago
and India, will maintain contact among team members.

Research
Although a modest endeavor compared to the enormous resources and efforts of major international cancer
initiatives and centers, our proposal has great potential to substantially impact cancer outcomes by integrating
and leveraging existing and complementary skills between UChicago and India. By bridging the two, we will be
able to link the genetic, genomic, and proteomic data that will be collected and analyzed for tumors within the
Indian population, with new advances, approaches, and tools being developed in real-time at UChicago and in
India to make cancer therapies combining drug targets with immunotherapies more effective and more
accessible for more patients.
In the first three years of our program, we will address the following challenges that currently limit the
application of drug and immunotherapy to larger cohorts of patients in both the US and India, including:
 Identifying predictive biomarkers and targets for personalized immunotherapy;
 Targeting host cells to modulate anti-tumor immunity and block metastatic progression;
 Developing accurate yet simple and low-cost means of detecting circulating tumor cells and tumorsecreted vesicles from blood to monitor disease progression and guide therapy; and
 Developing physiologically relevant tissue-engineered models of patient tumors to enable rapid,
effective, and personalized real-time screening of potential therapies.
6. Next steps
The India-UChicago Cancer Workshop on the Formation of a Strategic Partnership in Cancer Research between
India and the University of Chicago held in March, 2015 was extremely successful. As summarized above, not
only did the participants find common areas of interest, but they identified specific research questions and
challenges in breast and oral cancer that would benefit from a partnership by teams from UChicago and India.
Table 1 provides some details of possible teams of researchers for specific areas/cancer-types for engaging in
continued dialogue with a view of proposing and submitting joint grant proposals to Indian and international
funding agencies. It should be noted that the research of most participants cuts across the cancer types and
research areas listed. Future collaboration between UC and India researchers will emphasize themes that
apply to multiple cancer types to enhance the impact of the research outcome.
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To maintain the momentum and move forward on this initiative, it is important that we convene a
subsequent workshop that will be focused on Personalized Cancer Treatment based on innovative medical
genomics and immunotherapy. Our plan is to run a more focused meeting that will delve more deeply into the
science and form a basis for submission of funding proposals. To this end, we plan to submit an application for
another workshop sponsored by the UChicago Delhi center within the next few months.
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Table 1. Details of Teams to Engage in Research Areas/Cancer Types
Names of Researchers
Cancer-type/Research Area
India
University of Chicago
Marsha Rosner
Geoffrey Greene
Melody Swartz
Lev Becker
Tom Gajewski
Kevin White
Eileen Dolan
Everett Vokes
Ralph Weichselbaum
Diane Yamada
(Wokshop Participants only)
Paturu Kondaiah
Kartiki Desai
Geeta Mukherjee
Shubhada Chiplunkar
Rajiv Sarin
Radhakrishna Pillai
Breast Cancer
 Tumor heterogeneity
 Tumor microenvironment
 Immunengineering
 Regulators of ER+ and ER- breast cancers
Partha Majumder
Arindam Maitra
Binay Panda
Rajiv Sarin
Tapas Kundu
Susanta Roychoudhury
Sudhir Krishna
Sharmila Sengupta
Head and Neck Cancer
 Role of HPV and immune system
 Pre-malignant lesion genomics
 Role of inhibitors (such as Hat, Cox)
Cervical Cancer
 Immunomodulation in relation to HPV
vaccination
Rimas Lukas
Maciej Lesniak
Yamini Bakhtiar
Kumar Somasundaram
Subrata Sinha
Brain tumors
 Genomics and proteomics
 Inflammation and hypoxia
Wendy Stock
Michelle LeBeau
Mammen Chandy
Hematological Malignancies
Mary Ellen Geiger
Ben Glick
Dibyendu Bhattacharyya
Susanta Roychoudhury
Melody Swartz
Bob Grossman
Andrey Rzhetsky
Kevin White
Binay Panda
Partha Majumder
Mohandas Mallath

Advanced Imaging Technologies

Exosomes and circulating tumor cells

3D Cultures


Bionimbus
High-throughput computing
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PHOTO GALLERY
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The Group
K. VijayRaghavan
Partha Majumder
Marsha Rosner
Geoffrey Greene
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Melody Schwartz
Radhakrishna Pillai
Partha Majumder, Shubha Chiplunkar,
Geeta Mukherjee, Sharmila Sengupta
Paturu Kondaiah
Sharmila Sengupta
Subrata Sinha, Kevin White
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The Video Wall in the Lobby of the University of Chicago’s Delhi Center
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