Assistant Professor, Department of Molecular and Cellular Oncology, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX
Our research team is driven by a shared passion for unraveling the intricacies of gastrointestinal (GI) tract function and dysfunction. By employing state-of-the-art genetic techniques and physiologically relevant 3D cell culture models, we delve into both fundamental and translational biology questions related to GI pathogenesis. Our overarching objective is to pioneer innovative therapies that enhance patient outcomes and quality of life. Currently, our laboratory is focused on three key areas that we believe have the potential to revolutionize GI cancer research.
Firstly, we are dedicated to modeling gastric cancer using primary 3D organoids. Leveraging the power of CRISPR/Cas9 genome-editing technologies, we construct novel human gastric cancer models within 3D organoids. This pioneering approach allows us to investigate the underlying molecular mechanisms, oncogenic signaling pathways, and drug responses. By engineering tumor organoids that faithfully recapitulate various stages of gastric cancer, we strive to gain insights into tumor development, leading to potential strategies for cancer prevention and therapeutics.
Secondly, our research explores the intricate relationship between adult GI stem cells, cancer biology, and therapeutic approaches. The emergence of GI cancers involves dynamic changes in cell states, often accompanied by the dysregulation of signal pathways governing epithelial stem cell function and cell lineage differentiation. Through our investigations, we aim to elucidate how these dynamic changes contribute to tumor heterogeneity and uncover therapeutic vulnerabilities specific to cancer cells. Our ultimate goal is to advance the current understanding of cancer biology and develop new therapeutic strategies.
Lastly, we are actively engaged in studying the tumor microenvironment and the intricate interactions between tumors and the immune system. By developing advanced human 3D models that accurately replicate the stromal components of the tumor microenvironment ex vivo, we aim to address the unmet needs in the field of immuno-oncology. Through the creation of innovative 3D functional genomics platforms, we seek to enhance our understanding of how tumors interact with their microenvironment and gain profound insights into the complex processes underlying tumor-immune interactions.
In summary, our research team is committed to advancing the frontiers of GI cancer research through innovative approaches, ranging from modeling gastric cancer in 3D organoids to investigating adult GI stem cells and tumor microenvironment interactions. We aspire to make significant contributions to the field and drive the development of novel therapeutic strategies for improving patient outcomes.
|2017||Baylor College of Medicine, Houston, TX, USA, PHD, Integrative Molecular and Biomedical Sciences|
|2017-2023||Research Fellowship, Stanford University, Stanford, CA|
|2021||The NCI Pathway to Independence Award (K99/R00), NIH/NCI|
|2021||SCI Fellowship Award, Stanford Cancer Institute, Stanford Cancer Institute|
|2021||Scholar-in-Training Award, American Association for Cancer Research|
|2017||The Claude W. Smith Fellowship Award (Research), Baylor College of Medicine|
|2016||The NCI Predoctoral to Postdoctoral Fellow Transition Award (F99/K00), NIH/NCI|
|2016||The Dean’s Award of Excellence, Baylor College of Medicine|
|2015||The Claude W. Smith Fellowship Award (Academic), Baylor College of Medicine|
|2015||Professor John J. Trentin Scholarship Award, Baylor College of Medicine|
|2014||AGA Student Abstract Prize, AGA Research Foundation|
|2013||Robert and Emma Lou Cardell Foundation Fellowship, University of Cincinnati|
- Karlsson K, Przybilla MJ, Kotler E, Khan A, Xu H, Karagyozova K, Sockell A, Wong WH, Liu K, Mah A, Lo YH, Lu B, Houlahan KE, Ma Z, Suarez CJ, Barnes CP, Kuo CJ, Curtis C. Deterministic evolution and stringent selection during preneoplasia. Nature 618(7964):383-393, 2023. e-Pub 2023. PMID: 37258665.
- Dao V, Yuki K, Lo YH, Nakano M, Kuo CJ. Immune organoids: from tumor modeling to precision oncology. Trends Cancer 8(10):870-880, 2022. e-Pub 2022. PMID: 35773148.
- Lo YH, Kolahi KS, Du Y, Chang CY, Krokhotin A, Nair A, Sobba WD, Karlsson K, Jones SJ, Longacre TA, Mah AT, Tercan B, Sockell A, Xu H, Seoane JA, Chen J, Shmulevich I, Weissman JS, Curtis C, Califano A, Fu H, Crabtree GR, Kuo CJ. A CRISPR/Cas9-Engineered ARID1A-Deficient Human Gastric Cancer Organoid Model Reveals Essential and Nonessential Modes of Oncogenic Transformation. Cancer Discov 11(6):1562-1581, 2021. e-Pub 2021. PMID: 33451982.
- Lo YH, Karlsson K, Kuo CJ. Applications of Organoids for Cancer Biology and Precision Medicine. Nat Cancer 1(8):761-773, 2020. e-Pub 2020. PMID: 34142093.
- Han K, Pierce SE, Li A, Spees K, Anderson GR, Seoane JA, Lo YH, Dubreuil M, Olivas M, Kamber RA, Wainberg M, Kostyrko K, Kelly MR, Yousefi M, Simpkins SW, Yao D, Lee K, Kuo CJ, Jackson PK, Sweet-Cordero A, Kundaje A, Gentles AJ, Curtis C, Winslow MM, Bassik MC. CRISPR screens in cancer spheroids identify 3D growth-specific vulnerabilities. Nature 580(7801):136-141, 2020. e-Pub 2020. PMID: 32238925.
- Takashima S, Martin ML, Jansen SA, Fu Y, Bos J, Chandra D, O'Connor MH, Mertelsmann AM, Vinci P, Kuttiyara J, Devlin SM, Middendorp S, Calafiore M, Egorova A, Kleppe M, Lo Y, Shroyer NF, Cheng EH, Levine RL, Liu C, Kolesnick R, Lindemans CA, Hanash AM. T cell-derived interferon-γ programs stem cell death in immune-mediated intestinal damage. Sci Immunol 4(42), 2019. PMID: 31811055.
- Chen MS, Lo YH, Chen X, Williams CS, Donnelly JM, Criss ZK, Patel S, Butkus JM, Dubrulle J, Finegold MJ, Shroyer NF. Growth Factor-Independent 1 Is a Tumor Suppressor Gene in Colorectal Cancer. Mol Cancer Res 17(3):697-708, 2019. e-Pub 2019. PMID: 30606770.
- Santos AJM, Lo YH, Mah AT, Kuo CJ. The Intestinal Stem Cell Niche: Homeostasis and Adaptations. Trends Cell Biol 28(12):1062-1078, 2018. e-Pub 2018. PMID: 30195922.
- Gracz AD, Samsa LA, Fordham MJ, Trotier DC, Zwarycz B, Lo YH, Bao K, Starmer J, Raab JR, Shroyer NF, Reinhardt RL, Magness ST. Sox4 Promotes Atoh1-Independent Intestinal Secretory Differentiation Toward Tuft and Enteroendocrine Fates. Gastroenterology 155(5):1508-1523.e10, 2018. e-Pub 2018. PMID: 30055169.
- Zou WY, Blutt SE, Zeng XL, Chen MS, Lo YH, Castillo-Azofeifa D, Klein OD, Shroyer NF, Donowitz M, Estes MK. Epithelial WNT Ligands Are Essential Drivers of Intestinal Stem Cell Activation. Cell Rep 22(4):1003-1015, 2018. e-Pub 2018. PMID: 29386123.
- Lo YH, Noah TK, Chen MS, Zou W, Borras E, Vilar E, Shroyer NF. SPDEF Induces Quiescence of Colorectal Cancer Cells by Changing the Transcriptional Targets of β-catenin. Gastroenterology 153(1):205-218.e8, 2017. e-Pub 2017. PMID: 28390865.
- Almohazey D, Lo YH, Vossler CV, Simmons AJ, Hsieh JJ, Bucar EB, Schumacher MA, Hamilton KE, Lau KS, Shroyer NF, Frey MR. The ErbB3 receptor tyrosine kinase negatively regulates Paneth cells by PI3K-dependent suppression of Atoh1. Cell Death Differ 24(5):855-865, 2017. e-Pub 2017. PMID: 28304405.
- Lo YH, Chung E, Li Z, Wan YW, Mahe MM, Chen MS, Noah TK, Bell KN, Yalamanchili HK, Klisch TJ, Liu Z, Park JS, Shroyer NF. Transcriptional Regulation by ATOH1 and its Target SPDEF in the Intestine. Cell Mol Gastroenterol Hepatol 3(1):51-71, 2017. e-Pub 2016. PMID: 28174757.
- Lindemans CA, Calafiore M, Mertelsmann AM, O'Connor MH, Dudakov JA, Jenq RR, Velardi E, Young LF, Smith OM, Lawrence G, Ivanov JA, Fu YY, Takashima S, Hua G, Martin ML, O'Rourke KP, Lo YH, Mokry M, Romera-Hernandez M, Cupedo T, Dow L, Nieuwenhuis EE, Shroyer NF, Liu C, Kolesnick R, van den Brink MRM, Hanash AM. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 528(7583):560-564, 2015. e-Pub 2015. PMID: 26649819.
- Gilbert S, Nivarthi H, Mayhew CN, Lo YH, Noah TK, Vallance J, Rülicke T, Müller M, Jegga AG, Tang W, Zhang D, Helmrath M, Shroyer N, Moriggl R, Han X. Activated STAT5 confers resistance to intestinal injury by increasing intestinal stem cell proliferation and regeneration. Stem Cell Reports 4(2):209-25, 2015. e-Pub 2015. PMID: 25579133.
- Zhao H, Chen MS, Lo YH, Waltz SE, Wang J, Ho PC, Vasiliauskas J, Plattner R, Wang YL, Wang SC. The Ron receptor tyrosine kinase activates c-Abl to promote cell proliferation through tyrosine phosphorylation of PCNA in breast cancer. Oncogene 33(11):1429-37, 2014. e-Pub 2013. PMID: 23542172.
- Noah TK, Lo YH, Price A, Chen G, King E, Washington MK, Aronow BJ, Shroyer NF. SPDEF functions as a colorectal tumor suppressor by inhibiting β-catenin activity. Gastroenterology 144(5):1012-1023.e6, 2013. e-Pub 2013. PMID: 23376423.
- Lo YH, Ho PC, Wang SC. Epidermal growth factor receptor protects proliferating cell nuclear antigen from cullin 4A protein-mediated proteolysis. J Biol Chem 287(32):27148-57, 2012. e-Pub 2012. PMID: 22692198.
- Lo YH, Bell KN and Shroyer NF. Biology of intestinal epithelial stem cells. In: Intestinal Tumorigenesis, 2015.