The Mark Foundation Center for Advanced Genomics and Imaging


The Mark Foundation Center for Advanced Genomics and Imaging at the Johns Hopkins University (JHU) brings together the tools of astronomy image analysis, pathology, computer science, cancer genomics, and immunogenomics to solve problems in oncology and find innovative solutions that can expand the number of cancer patients who benefit from immunotherapy.

Scientists from The Mark Foundation collaborate with JHU researchers as part of a joint steering committee that reviews scientific progress and facilitate the success of the center. The Mark Foundation Center for Advanced Genomics and Imaging is led by Drew Pardoll, MD, PhD, Director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy and co-Director of the Cancer Immunology Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, together with Janis Taube, MD, MSc, Professor of Dermatology and Pathology and Director of the Division of Dermatopathology and co-Director of the Tumor Microenvironment Laboratory of the Bloomberg~Kimmel Institute for Cancer Immunotherapy, and Alexander Szalay, PhD, a Bloomberg Distinguished Professor in the Department of Physics and Astronomy; .

Building on the MANAFEST project begun in December 2017 with support from both the Bloomberg~Kimmel Institute and The Mark Foundation for Cancer Research, the center has expanded its focus on platforms for identifying cancer immunotherapy biomarkers, leveraging innovative technologies in cancer genomics, immune cell profiling, and digital pathology. The overarching goal is to facilitate the development of biomarkers that can more accurately predict which patients will benefit from a given immunotherapy, a centerpiece of Kimmel Cancer Center’s precision therapy vision.

Astronomy accelerates pathology

One pillar of the center was the creation of a new platform called AstroPath that takes a model used in astronomy and turns into one that can be used for massively scalable, spatially resolved analysis of the tumor immune microenvironment. Using AstroPath, Taube and astrophysicist Alexander Szalay, Ph.D., a Bloomberg Distinguished Professor of Physics and Astronomy, lead ongoing research that applies the technology used to ascertain the position of galaxies to the spatial relations in the tumor microenvironment. AstroPath’s groundbreaking celestial mapping algorithms can analyze hundreds of millions of cells, so researchers receive a detailed picture of the tumor’s location in the body and how it reacts with surrounding tissues.

Towards a unified platform for cancer genomics and cancer immunology

The other pillar of the center is the MANAFEST platform, which is focused on the development of a system to identify immune responses to changes in the genomes of cancer cells that could be used as a basis for personalized immunotherapy. Mutations, which represent changes in cancer genomes, generate biochemical signatures that are recognized as foreign by the immune system. The identification of such fragments, known as mutation-associated neoantigens (MANA), and the immune cells which target them for killing, is the goal of the MANAFEST platform. To accomplish this goal, cancer genomics and immunology analyses are integrated within a single, standardized platform that enables the identification of key biological indicators of how cancer patients will respond to immunotherapies. This integration represents a collaboration between the cancer immunology and cancer genetics programs, led by Drs. Bert Vogelstein and Ken Kinzler, Professors of Oncology and co-directors of the Ludwig Center for cancer genomics.

A renewed commitment

In 2022, The Mark Foundation for Cancer Research and the Bloomberg~Kimmel Institute for Cancer Immunotherapy (BKI) announced a $10 million commitment at to continue to fund novel work and advance immunotherapy research to provide lifesaving breakthroughs to people with cancer.

“Cancer treatment is advancing every day, and immunotherapy is a big reason for that,” said Michael R. Bloomberg, founder of Bloomberg LP and Bloomberg Philanthropies and founding donor of the Bloomberg~Kimmel Institute for Cancer Immunotherapy. “By teaming up with The Mark Foundation, this new investment will build on the cutting-edge work that Johns Hopkins and its partners are leading — saving lives and bringing us closer to bigger breakthroughs.”

“In less than three years, The Mark Foundation Center at Johns Hopkins University has made outstanding progress in improving our knowledge of how tumors respond to immunotherapy,” said Ryan Schoenfeld, chief executive officer of The Mark Foundation for Cancer Research. “Our collaboration with the Bloomberg~Kimmel Institute allows us to develop the next-generation genomics and imaging platforms for cancer immunotherapy necessary to save lives. We believe that over the next five years, the number of cancer patients who will benefit will burgeon.”

Investigators

Paul Rothman, MD, Dean and CEO of Johns Hopkins Medicine, and an esteemed group of scientists, bring focused leadership to the new Center: Robert Anders, MD, PhD, Associate Professor of Pathology and co-Director of the Tumor Microenvironment Laboratory of the Bloomberg-Kimmel Institute for Cancer Immunotherapy with Dr. Taube; Alan Yuille, PhD, a Bloomberg Distinguished Professor in the Departments of Cognitive Science and Computer Science;  Alexander Baras, MD, PhD Associate Professor of Pathology; and Srinivasan Yegnasubramanian, MD, PhD, Associate Professor of Oncology.

PUBLISHED RESEARCH

Danilova L, Anagnostou V, Caushi JX, Sidhom JW, Guo H, Chan HY, Suri P, Tam A, Zhang J, Asmar ME, Marrone KA, Naidoo J, Brahmer JR, Forde PM, Baras AS, Cope L, Velculescu VE, Pardoll DM, Housseau F, Smith KN. The Mutation-Associated Neoantigen Functional Expansion of Specific T Cells (MANAFEST) Assay: A Sensitive Platform for Monitoring Antitumor Immunity. Cancer Immunol Res. 2018.

Smith KN, Llosa NJ, Cottrell TR, Siegel N, Fan H, Suri P, Chan HY, Guo H, Oke T, Awan AH, Verde F, Danilova L, Anagnostou V, Tam AJ, Luber BS, Bartlett BR, Aulakh LK, Sidhom JW, Zhu Q, Sears CL, Cope L, Sharfman WH, Thompson ED, Riemer J, Marrone KA, Naidoo J, Velculescu VE, Forde PM, Vogelstein B, Kinzler KW, Papadopoulos N, Durham JN, Wang H, Le DT, Justesen S, Taube JM, Diaz LA Jr, Brahmer JR, Pardoll DM, Anders RA, Housseau F. Persistent mutant oncogene specific T cells in two patients benefitting from anti-PD-1. J Immunother Cancer. 2019.

Llosa NJ, Luber B, Tam AJ, Smith KN, Siegel N, Awan AH, Fan H, Oke T, Zhang J, Domingue J, Engle EL, Roberts CA, Bartlett BR, Aulakh LK, Thompson ED, Taube JM, Durham JN, Sears CL, Le DT, Diaz LA, Pardoll DM, Wang H, Anders RA, Housseau F. Intratumoral Adaptive Immunosuppression and Type 17 Immunity in Mismatch Repair Proficient Colorectal Tumors. Clin Cancer Res. 2019.

Anagnostou V, Niknafs N, Marrone K, Bruhm DC, White JR, Naidoo J, Hummelink K, Monkhorst K, Lalezari F, Lanis M, Rosner S, Reuss JE, Smith KN, Adleff V, Rodgers K, Belcaid Z, Rhymee L, Levy B, Feliciano J, Hann CL, Ettinger DS, Georgiades C, Verde F, Illei P, Li QK, Baras AS, Gabrielson E, Brock MV, Karchin R, Pardoll DM, Baylin SB, Brahmer JR, Scharpf RB, Forde PM, Velculescu VE. Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer. Nat Cancer. 2020.

Topalian SL, Taube JM, Pardoll DM. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science. 2020.

Stein JE, Lipson EJ, Cottrell TR, Forde PM, Anders RA, Cimino-Mathews A, Thompson ED, Allaf ME, Yarchoan M, Feliciano J, Wang H, Jaffee EM, Pardoll DM, Topalian SL, Taube JM. Pan-Tumor Pathologic Scoring of Response to PD-(L)1 Blockade. Clin Cancer Res. 2020.

Zhang J, Ji Z, Caushi JX, El Asmar M, Anagnostou V, Cottrell TR, Chan HY, Suri P, Guo H, Merghoub T, Chaft JE, Reuss JE, Tam AJ, Blosser RL, Abu-Akeel M, Sidhom JW, Zhao N, Ha JS, Jones DR, Marrone KA, Naidoo J, Gabrielson E, Taube JM, Velculescu VE, Brahmer JR, Housseau F, Hellmann MD, Forde PM, Pardoll DM, Ji H, Smith KN. Compartmental Analysis of T-cell Clonal Dynamics as a Function of Pathologic Response to Neoadjuvant PD-1 Blockade in Resectable Non-Small Cell Lung Cancer. Clin Cancer Res. 2020.

Topalian SL, Bhatia S, Amin A, Kudchadkar RR, Sharfman WH, Lebbé C, Delord JP, Dunn LA, Shinohara MM, Kulikauskas R, Chung CH, Martens UM, Ferris RL, Stein JE, Engle EL, Devriese LA, Lao CD, Gu J, Li B, Chen T, Barrows A, Horvath A, Taube JM, Nghiem P. Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial. J Clin Oncol. 2020.

Anagnostou V, Bruhm DC, Niknafs N, White JR, Shao XM, Sidhom JW, Stein J, Tsai H, Wang H, Belcaid Z, Murray J, Balan A, Ferreira L, Macdonald P, Rotolo M, Baras A, Taube J, Karchin R, Scharpf R, Grasso C, Ribas A, Pardoll D, Topalian S, Velculescu V. Integrative Tumor and Immune Cell Multi-omic Analyses Predict Response to Immune Checkpoint Blockade in Melanoma. Cell Reports Med. 2020.

Hsiue EH, Wright KM, Douglass J, Hwang MS, Mog BJ, Pearlman AH, Paul S, DiNapoli SR, Konig MF, Wang Q, Schaefer A, Miller MS, Skora AD, Azurmendi PA, Murphy MB, Liu Q, Watson E, Li Y, Pardoll DM, Bettegowda C, Papadopoulos N, Kinzler KW, Vogelstein B, Gabelli SB, Zhou S. Targeting a neoantigen derived from a common TP53 mutation. Science. 2021.

Douglass J, Hsiue EH, Mog BJ, Hwang MS, DiNapoli SR, Pearlman AH, Miller MS, Wright KM, Azurmendi PA, Wang Q, Paul S, Schaefer A, Skora AD, Molin MD, Konig MF, Liu Q, Watson E, Li Y, Murphy MB, Pardoll DM, Bettegowda C, Papadopoulos N, Gabelli SB, Kinzler KW, Vogelstein B, Zhou S. Bispecific antibodies targeting mutant RAS neoantigens. Sci Immunol. 2021.

Pearlman AH, Hwang MS, Konig MF, Hsiue EH, Douglass J, DiNapoli SR, Mog BJ, Bettegowda C, Pardoll DM, Gabelli SB, Papadopoulos N, Kinzler KW, Vogelstein B, Zhou S. Targeting public neoantigens for cancer immunotherapy. Nat Cancer. 2021.

Berry S, Giraldo NA, Green BF, Cottrell TR, Stein JE, Engle EL, Xu H, Ogurtsova A, Roberts C, Wang D, Nguyen P, Zhu Q, Soto-Diaz S, Loyola J, Sander IB, Wong PF, Jessel S, Doyle J, Signer D,Wilton R, Roskes JS, Eminizer M, Park S, Sunshine JC, Jaffee EM, Baras A, De Marzo AM, Topalian SL, Kluger H, Cope L, Lipson EJ, Danilova L, Anders RA, Rimm DL, Pardoll DM, Szalay AS, Taube JM. Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade. Science. 2021.

Cottrell T, Zhang J, Zhang B, Kaunitz GJ, Burman P, Chan HY, Verde F, Hooper JE, Hammers H, Allaf ME, Ji H, Taube J, Smith KN. Evaluating T-cell cross-reactivity between tumors and immune-related adverse events with TCR sequencing: pitfalls in interpretations of functional relevance. J Immunother Cancer. 2021.

Taube JM, Roman K, Engle EL, Wang C, Ballesteros-Merino C, Jensen SM, McGuire J, Jiang M, Coltharp C, Remeniuk B, Wistuba I, Locke D, Parra ER, Fox BA, Rimm DL, Hoyt C. Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study. J Immunother Cancer. 2021.

Caushi JX, Zhang J, Ji Z, Vaghasia A, Zhang B, Hsiue EHC, Mog BJ, Hou W, Justesen S, Blosser R, Tam A, Anagnostou V, Cottrell TR, Guo H, Chan HY, Singh D, Thapa S, Dykema AG, Burman P, Choudhury B, Aparicio L, Cheung LS, Lanis M, Belcaid Z, El Asmar M, Illei PB, Wang R, Meyers J, Schuebel K, Gupta A, Skaist A, Wheelan S, Naidoo J, Marrone KA, Brock M, Ha J, Bush EL, Park BJ, Bott M, Jones DR, Reuss JE, Velculescu VE, Chaft JE, Kinzler KW, Zhou S, Vogelstein B, Taube JM, Hellmann MD, Brahmer JR, Merghoub T, Forde PM, Yegnasubramanian S, Ji H, Pardoll DM, Smith KM. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature. 2021.

Giraldo NA, Berry S, Becht E, Ates D, Schenk KM, Engle EL, Green B, Nguyen P, Soni A, Stein JE, Succaria F, Ogurtsova A, Xu H, Gottardo R, Anders RA, Lipson EJ, Danilova L, Baras AS, Taube JM. Spatial UMAP and Image Cytometry for Topographic Immuno-oncology Biomarker Discovery. Cancer Immunol Res. 2021.

Ozbek B, Ertunc O, Erickson A, Vidal ID, Gomes-Alexandre C, Guner G, Hicks JL, Jones T, Taube JM, Sfanos KS, Yegnasubramanian S, De Marzo AM. Multiplex immunohistochemical phenotyping of T cells in primary prostate cancer. Prostate. 2022.

Almodovar Cruz GE, Kaunitz G, Stein JE, Sander I, Hollmann T, Cottrell TR, Taube JM, Sunshine JC. Immune cell subsets in interface cutaneous immune-related adverse events (cirAEs) associated with anti-PD-1 therapy resemble acute graft vs host disease more than lichen planus. J Cutan Pathol. 2022.

Cook AL, Wyhs N, Sur S, Ptak B, Popoli M, Dobbyn L, Papadopoulos T, Bettegowda C, Papadopoulos N, Vogelstein B, Zhou S, Kinzler KW. An isogenic cell line panel for sequence-based screening of targeted anticancer drugs. iScience. 2022.

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