Lan Zhou, M.D., Ph.D.

Assistant Professor

Mailing Address:
2103 Cornell Rd.
WRB 6527
Cleveland, OH 44106-7288

phone: (216) 368-1671
fax: (216) 368-0494
email: Lan.Zhou@Case.edu

Biography
Dr. Lan Zhou earned her M.D. from Shanghai Medical University in 1991. She then spent two years at the Graduate School of Shanghai Medical University, Department of Biochemistry. The next six years were spent at State University of New York at Buffalo, NY, where she received her Ph.D. in Molecular and Cell Biology. While a graduate student, she studied gap junction protein regulation by Src oncogene. She then joined the lab of Dr. John Lowe in the Howard Hughes Medical Institute, University of Michigan. While in Dr John Lowe’s lab, she worked on Notch fucosylation modification in hematopoiesis. She then started her Clinical Pathology Residency training in 2001 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, and she has clinical services in Transfusion Medicine since. She became the Director of the Molecular Diagnostic Laboratory at University Hospitals Case Medical Center (UHCMC) 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.

Research
The research in Dr Zhou’s laboratory focuses on Notch in hematopoiesis and in cancer biology. Since 2005, her research is devoted to understanding how fucosylation affects Notch-dependent regulation of hematopoietic stem cell proliferation, early myeloid lineage specification and hematopoietic stem cell niche maintenance. Dr. Zhou’s long term research goals include, 1) explore the role of Notch/Hes1 in colon epithelial homeostasis, immunity, and colon carcinogenesis in the serrated pathway; 2) define mechanism(s) by which Notch functions as a signaling molecule and an adhesion molecule in HSC niche lodgement, maintenance, and in stem cell mobilization; 3) explore molecular and cellular regulations of leukemia microenvironment and the role of Notch in leukemia and tumor micro-environment; 4) develop a deeper understanding of several pancreatic cancer biomarkers, including PrP, Notch1, and CRABP-II, and their physiological significance in pancreatic cancer progression and metastasis. Her research utilizes a combination of animal models and human tissue and cancer specimens. Dr Zhou’s clinical research focuses on the application of cutting-edge molecular diagnostic tools in infectious diseases, transfusion medicine, solid tumors and hematologic neoplasms.

Publications
Zhou, L., Kasperak, E.M., Nicholson, B.J. (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, and 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., and 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., and 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 Pathology June 45(6):1177-83

Yu, V. W. C., Saez, B., Lotinun,S., Cook,C., Rusuf, R.Z., Ferraro,F., Lymperi,S., Wang,Y., Pardo-Saganta, A., Raaijmakers, M.G.P., Wu, J.Y., Zhou, L.,Rajagopal, J., Kronenberg, H.M.,  Baron,R., Scadden, D.T.  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, T.J., Riquelme, P., Rastrojo, A., Aguado, B., Stein-Streilein, J., Tanaka, M., Zhou, L., Zhang, J., Lowary, T., Ginhoux, F., Park, C.G., Cheolho, C., Brody, J., Turley, S., Lira, S., Bronte, V., Gordon, S., Heeger, P., Merad, M., Hutchinson, J., Chen, S., and Jordi Ochando. 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, A.Y., Zhou, L. Aberrant Notch Signaling in Acute Lymphoblastic Leukemia Marrow Suppresses Osteoblasts and Inhibits Hematopoietic Niche Function. Cancer Research 2016Mar 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., and Zhou. L. Fucosylation-deficiency leads to colitis and adenocarcinoma via serrated-like lesion intermediates. Gastroenterology (in revision). 2016