Siyuan Zhang, M.D., Ph.D. - Faculty Profile

Biography

Exploring the co-evolution between tumor cells and tumor microenvironment is the central theme of my laboratory. Using the state-of-art single cell level sequencing and multiphoton based intravital imaging, we aim to reveal the in-depth molecular mechanisms of tissue dynamics during the early tumor development, drug resistance and metastasis colonization. Base on our pre-clinical findings, we also conduct pre-clinical testing of novel combinatorial therapies to overcome drug resistance and prevent tumor metastasis.

We are focusing on perfecting in vivo model system and integrating innovative approaches to faithfully model and investigate dynamic interaction between tumor and its tumor microenvironment at single cell level. We have developed intravital multiphoton imaging and tissue clearing-based whole tissue imaging techniques, which allow us to explore the spatiotemporal dynamics of tumor and tumor microenvironment in situ at cellular and subcellular level. We have also established single cell-based RNA-seq pipeline, which enables us to map the single cell level transcriptome dynamics at the early tumor development and metastatic colonization. We aim to tackle the overarching challenge of studying early tumor/metastasis development in situ and gain unprecedented mechanistic insights of the role of tumor microenvironment during the cancer progression in its native pathophysiological microenvironment. Three specific research themes in my laboratory are:

1. What are the critical changes during the first moment of metastatic seeding and colonization? Can we exploit those changes as novel therapy to prevent metastatic outgrowth?

2. How heterogeneous tumor responses to environmental stress, such as drug treatment, differently? How the tumor microenvironment primes “seemingly” normal tissue and promotes an accelerated tumor development and acquired drug resistance?

3. Can we systematically delineate tumor and tumor microenvironment genetically and morphologically in situ?

For more information, go to S.Zhang Lab website: https://www.curiosityrover.org

Research Interest

Cancer metastasis
Neuroinflammation
Single cell genomics
Tumor immunology
Tumor microenvironment

Publications

Featured Publications

Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype.: Bahcecioglu G, Yue X, Howe E, Guldner I, Stack MS, Nakshatri H, Zhang S, Zorlutuna P, Adv Sci (Weinh) 2021 11 8 22 e2100128
Isolation of mouse brain-infiltrating leukocytes for single cell profiling of epitopes and transcriptomes.: Guldner IH, Golomb SM, Wang Q, Wang E, Zhang S, STAR Protoc 2021 06 2 2 100537
Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis.: Golomb SM, Guldner IH, Zhao A, Wang Q, Palakurthi B, Aleksandrovic EA, Lopez JA, Lee SW, Yang K, Zhang S, Cell Rep 2020 12 33 9 108438
CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10.: Guldner IH, Wang Q, Yang L, Golomb SM, Zhao Z, Lopez JA, Brunory A, Howe EN, Zhang Y, Palakurthi B, Barron M, Gao H, Xuei X, Liu Y, Li J, Chen DZ, Landreth GE, Zhang S, Cell 2020 11 183 5 1234-1248.e25
Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth.: Howe EN, Burnette MD, Justice ME, Schnepp PM, Hedrick V, Clancy JW, Guldner IH, Lamere AT, Li J, Aryal UK, D'Souza-Schorey C, Zartman JJ, Zhang S, Nat Commun 2020 06 11 1 3017
Single-cell profiling guided combinatorial immunotherapy for fast-evolving CDK4/6 inhibitor-resistant HER2-positive breast cancer.: Wang Q, Guldner IH, Golomb SM, Sun L, Harris JA, Lu X, Zhang S, Nat Commun 2019 Aug 10 1 3817
Death effector domain-containing protein induces vulnerability to cell cycle inhibition in triple-negative breast cancer.: Ni Y, Schmidt KR, Werner BA, Koenig JK, Guldner IH, Schnepp PM, Tan X, Jiang L, Host M, Sun L, Howe EN, Wu J, Littlepage LE, Nakshatri H, Zhang S, Nat Commun 2019 Jun 10 1 2860
Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth.: Zhang L, Zhang S, Yao J, Lowery FJ, Zhang Q, Huang WC, Li P, Li M, Wang X, Zhang C, Wang H, Ellis K, Cheerathodi M, McCarty JH, Palmieri D, Saunus J, Lakhani S, Huang S, Sahin AA, Aldape KD, Steeg PS, Yu D Nature 2015 Oct
Targeting Src family kinases in anti-cancer therapies: turning promise into triumph.: Zhang S, Yu D, Trends Pharmacol Sci 2012 Mar 33 3 122-8
Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways.: Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW, Xiong Y, Tseng LM, Li SH, Ding Z, Sahin AA, Esteva FJ, Hortobagyi GN, Yu D, Nat Med 2011 Apr 17 4 461-9

Honors & Awards

Faculty Excellence in Research Award
Biological Sciences, University of Notre Dame (2020)
Outstanding Investigator Award
SCBA Annual Symposium (2019)
Bristol-Myers Squibb Award for Clinical/Translational Research
Bristol-Myers Squibb (2011)

Professional Associations/Affiliations

Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana (2012-2018)
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana (2018-2022)
Department of Community, Occupational and Family Medicine, National University of Singapore, Republic of Singapore (2001-2005)
Department of Community, Occupational and Family Medicine, National University of Singapore, Republic of Singapore (2005-2006)
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (2007-2012)
Department of Pathology, UT Southwestern Medical Center, Dallas, Texas (2022)
Department of Toxicology, Peking University Health Science Center, Beijing, PR China (1998-2000)
Peking University Health Science Center, Beijing, PR China (1993-1998)