Dr. Lan Zhou earned her MD from Shanghai Medical University in 1991. Dr. Zhou then received her PhD in Molecular and Cell Biology from State University of New York at Buffalo, NY. While a graduate student, she studied gap junction protein regulation by Src oncogene. She then joined the lab of Dr. John Lowe for postdoctoral training in the Howard Hughes Medical Institute, University of Michigan, where she worked on Notch fucosylation modification in hematopoiesis. She completed her Clinical Pathology Residency training followed by Transfusion Medicine Fellowship training at University of Michigan Hospitals. In 2005, Dr. Zhou joined Case Western Research University School of Medicine in the Department of Pathology as an Assistant Professor. She became the Director of the Molecular Diagnostic Laboratory at University Hospitals Cleveland Medical Center in 2007. She is currently an Associate Professor with tenure. Dr. Zhou is board certified in American Board of Clinical Pathology/Transfusion Medicine and American Board of Molecular Genetic Pathology.
My labs studies Notch signaling in stress hematopoiesis, hematopoietic stem cell niche, and leukemia microenvironment. Additional projects include pathogenesis of inflammation-associated colorectal cancer mouse models and targeting pancreatic cancer metabolic vulnerability and drug resistance.
The research in Dr. Zhou’s laboratory focuses on Notch in hematopoiesis and in cancer biology.
Dr. Zhou’s long term research goals include:
- Define the mechanism(s) of which Notch2 regulates hematopoietic stem cell (HSC) quiescence, niche retention and egress
- Develop a Notch- ligand targeting strategy to facilitate HSC mobilization and to improve HSC activity in hematopoietic cell therapy
- Define the significance of fucosylglycans in the pathogenesis of colitis
- Define the role of Hes1 in colon epithelial homeostasis, immunity, and carcinogenesis
- Explore the function of aberrant Notch signaling in leukemia micro-environment;
- Develop a deeper understanding of pathophysiology of pancreatic cancer biomarkers (including PrP, Notch, and CRABP-II) in pancreatic cancer metabolism, metastasis and chemo-resistance.
Her research employs a combination of tools including genetically modified animal models, glycomics, state-of-the-art intravital microscopy, scRNA-seq, pre-clinical models of mobilization and transplantation, and digital RNA counting and spatial profiling of human cancer tissues. Dr. Zhou’s clinical research focuses on the application of cutting-edge molecular diagnostic tools in infectious diseases and transfusion medicine.
- Zhou L, Kasperak EM, Nicholson BJ. (1999) Dissection of the molecular basis of pp60v-src induced gating of connexin 43 gap junctions. Journal Cell Biology. 144 (5): 1033-1045.
- Zhou L, Giacherio D, Cooling L, Davenport RD. Use of B-natriuretic peptide as a diagnostic marker in the differential diagnosis of transfusion-associated circulatory overload. Transfusion. 2005 Jul;45(7):1056-63.
- Zhou L, Wei LL, Yan Q, Petryniak B, Man Y, Su C, Shim J, Chervin S, Lowe JB. Notch-dependent control of myelopoiesis is regulated by fucosylation. Blood. 2008 Jul 15;112(2):308-19. * Comment in Blood. 2008 Jul 15;112(2):214-5: “Unsweetened Notch leads to myeloproliferation”.
- Yan Q, Yao D, Wei L, Huang Y, Zhang L, Xin W, Shin J, Man Y, Gerson S, Lowe J, Zhou L. O-fucose Modulates Notch-Controlled Lineage Commitment. American Journal of Pathology. 2010 June 176 (6): 2921-2934.
- Myers J, Huang Y, Wei L, Yan Q, Huang A, Zhou L. Fucose-Deficient Hematopoietic Stem Cells Have Decreased Self-Renewal and Aberrant Marrow Niche Occupancy. Transfusion. 2010 Dec 50(12):2660-9.
- Yao D, Huang Y, Huang X, Wang W, Yan Q, Wei L, Xin W, Myers J, Lowe J, Gerson S, Staley P, Zhou L. Protein of O-Fucosyltransferase 1 (Pofut1) Regulates Lymphoid and Myeloid Homeostasis through Modulation of Notch Receptor Ligand Interactions. Blood. 2011 May 26;117(21):5652-62.
- Xiao W, Hong H, Awadallah A, Zhou L, Xin W. Utilization of CDX2 Expression in Diagnosing Pancreatic Ductal Adenocarcinoma and Predicting Prognosis. 2014 PLoS ONE 9(1): e86853. doi:10.1371/journal.pone.0086853
- Xiao W, Hong H, Awadallah A, Yu S, Zhou L, Xin W. CRABP-II is a highly sensitive and specific diagnostic molecular marker for pancreatic ductal adenocarcinoma in distinguishing from benign pancreatic conditions. 2014 Human PathologyJune 45(6):1177-83
- Yu V.WC, Saez B, Lotinu S, Cook C, Rusuf RZ, Ferraro F, Lymper S, Wang Y, Pardo-Saganta A, Raaijmakers MGP, Wu JY, Zhou L, Rajagopal J, Kronenberg HM, Baron R, Scadden DT. Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow. J Exp Med. 2015 May 4;212(5):759-74.
- Wang W, Yu S, Myers J, Wang Y, Huang X, Zimmerman G, Huang D, Shim J, Yu V, Huang Y, Xin W, Qiao P, Yan M, Scadden D, Lowe J, Xin W, Huang A, Stanley P, Siebel C, Zhou L. Notch Receptor-Ligand Engagement Maintains Hematopoietic Stem Cell Quiescence and Niche Retention. Stem Cells. 2015 Jul;33(7):2280-93
- Conde P, Rodriguez M, van der Touw W, Burns M, Miller J, Brahmachary M, Chen H, Boros P, Rausell-Palamos F, Yun TJ, Riquelme P, Rastrojo A, Aguado B, Stein-Streilein J, Tanaka M, Zhou L, Zhang J, Lowary T, Ginhoux F, Park, CG, Cheolho C, Brody J, Turley S, Lira S, Bronte V, Gordon S, Heeger P, Merad M, Hutchinson J, Chen S, Ochando J. DC-SIGN+ Macrophages Control the Induction of Transplantation Tolerance. Immunity. 2015 Jun 16;42(6):1143-58.
- Cui M, Awadallah A, Liu W, Zhou L, Xin W. Loss of Hes1 Differentiates Sessile Serrated Adenoma/Polyp from Hyperplastic Polyp. American Journal of Surgical Pathology 2016;40:113-9.
- Wang W, Zimmerman G, Huang X, Yu S, Myers J, Wang Y, Moreton S, Nthale J, Awadallah A, Beck R, Xin W, Wald D, Huang AY, Zhou L. Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function. Cancer Research 2016 Mar 15;76(6):1641-52.
- Wang Y, Huang D, Cui M, Chen K, Wang W, Huang X, Amadellah A, Li Q, Friedman A, Di Martino L, Cominelli F, Miron A, Chan R, Shen X, Fox J, Yan X,Kalady M, Markowitz S, Maillard I, Lowe J, Xin W, Zhou L. Fucosylation-deficiency leads to colitis and adenocarcinoma via serrated-like lesion intermediates. Gastroenterology (in revision). 2016
- Wang W, Yu S, Myers J, Wang Y, Xin WW, Albakri M, Xin A, Li M, Huang AY, Xin W, Siebel CW, Lazarus HM, Zhou L. Notch2 Blockade Enhances Hematopoietic Stem Cell Mobilization and Subsequent Engraftment. Hematologica. 2017; Oct;102(10):1785-1795.
- Kong G, You X, Wen Z, Chang YI, Loh M, Hofmann I, Yang D, Zhong X, Padron E, Zhou L, Pear WS, Zhang J. Downregulating Notch counteracts KrasG12D-induced ERK activation and oxidative phosphorylation in myeloproliferative neoplasm. Leukemia 2019 Mar;33(3):671-685