Cancer Research Scientist

Resume of Gang Liu, PhD ****

- * -

Email: ***********@*****.*** Phone: 714-***-****

Visa Type: Lawful Permanent Resident of the United States DOB: 09/21/1978 Education Background

Name of University orAcademy Location Major Subject Degree Dates Received Academy of Military Medical

Sciences

Beijing, China Cancer Research Doctorate 07/2007

Academy of Military Medical

Sciences

Beijing, China Cell Biology Masterate 07/2002

Anhui Normal University Wuhu, China Biology Baccalaureate 07/1999 Work Experience

1. May 2011-March 2015: Assistant specialist in University of California, Irvine, USA. 2. May 2009-April 2011: Postdoctoral Fellow in the Children’s Hospital Los Angeles, University of Southern California, USA.

3. May 2008-April 2009: Postdoctoral Fellow in School of Medicine, University of South Carolina, USA.

4. August 2002-July 2004: Assistant Professor in Beijing Military Medical College, China. Summary of Major Research Achievements

1. My research and achievements in cancer metabolism based cancer chemotherapeutics. Cancer cell demands huge extracellular nutrient uptake via nutrient transporters located in cell membrane to satisfy its hyperactive anabolism and uncontrolled proliferation, which makes cancer metabolism a promising target for typical cancer therapeutics. FTY720, a sphingolipid-based drug, can trigger loss of nutrient transporters on cell membrane, and selectively starve cancer cells, but causes a decrease in heart rate.

My projects are designed to evaluate novel FTY720 analogues that wipe off the toxicity but retain both the effects on transporters and the excellent pharmacologic properties of FTY720, and to elucidate the mechanism(s) of how FTY720 and its analogues induce transporters withdrawal from cell membrane. While several derivatives of FTY720 are found to have the ability to selectively starve cancer cells, my work has revealed that PP2A is involved in FTY720 and its analogues induced nutrient transporter loss. 2. My findings in research of cancer metabolism targeted cancer therapeutics. My research indicated that loss of TSC2 confers resistance to ceramide and nutrient deprivation. In low amino acid and glucose medium, and following ceramide-induced nutrient transporter loss, elevated mTORC1 activity significantly enhanced the adaptive upregulation of new transporter proteins for amino acids and glucose. And the introduction of oncogenic Ras abrogated the survival advantage of TSC2 / MEFs upon ceramide treatment most likely by increasing nutrient demand. These results suggest that, in the absence of oncogene-driven biosynthetic demand, mTORC1-dependent translation facilitates the adaptive cellular response to nutrient stress. 3. My achievements in cancer stem cell research.

Latest research demonstrates that, except residue of cancer cells that survive cancer treatment, it can also be cancer stem cells that initiate cancer recurrence in patients, leading to cancer treatment failure. Resume of Gang Liu, PhD 2017

- 2 -

Therefore it is crucial to elucidate the mechanism of cancer stem cell development and find the markers that will identify cancer stem cell. My major contributions to this area are exemplified as below: 1) My study implicated MAT1 in hematopoietic stem cell proliferation and leukemia progression. My results suggested that MAT1 overexpression resisted intrinsic MAT1 fragmentation to sustain hematopoietic CD34+ cell expansion while preventing granulopoiesis, suggesting that the intrinsically programmed MAT1 expression and fragmentation regulate granulopoiesis by inversely coordinating CAK and TFIIH activities.

2) My findings unveiled KLF4’s role in cancer initiation. My study showed that active KLF4 resulted in increased gastrointestinal tract stem cells, and tumor repressors weakened KLF4- mediated activation of cell proliferation. This original finding identified KLF4’s role in both cancer initiation and tissue stem cell potential maintenance. 3) My work contributed to identification of osteosarcoma cancer stem cells. My findings identified that the CD49f CD133+ subpopulation were enriched in osteosarcoma cancer stem cells that are responsible for osteosarcoma initiation. My contributions provided the opportunity for development of osteosarcoma cancer stem cells-targeted therapy aimed at osteosarcoma eradication.

4) My research identified 2 metastasis-associated genes. Cancer stem cells have strong potential of initiating cancer cell invasion and metastasis. I identified 2 novel genes, mag-1 and mag-2, whose functions were closely associated with cancer invasion and metastasis phenotypes. My contributions to this research helped shed on mechanism underlying tumor metastasis. 4. My achievements in leukemia research.

Leukemia treatment through transplantation is always badly frustrated by the shortage of hematopoietic stem cells (HSCs) existing in graft transplanted into leukemia patients and the graft-versus- host disease (GVHD) resulting from graft attacking recipient’s tissues. Results of my projects aimed to solve the problems showed that HSCs, with the support of bone marrow stromal cells, were extensively expanded while the multi-potent, naive HSCs were maintained. My further research indicated that, for the first time, mesenchymal stem cells (MSCs) play similar roles as stromal cells in supporting HSCs expansion, and that MSCs unexpectedly inhibit lymphocyte differentiation from HSCs. Laboratory Skills

Molecular Biology

Plasmid subcloning; DNA or RNA extraction; PCR and Real-time PCR; RNAi; ChIP assay; Luciferase assay.

Cell Biology

Cell culture; Gene transfection; Lenti/retrovirus production and transduction; Subcellular localization; MTTAssay; Intracellular cell staining; FACS; Immunofluorescence staining. Protein Experiment

Prokaryotic expression; Preparation of polyclonal antibody; Western blot; Co-IP. Biochemistry

ELISA; Agarose gel electrophoresis; SDS-PAGE; Western Blotting. Bioinformatics

Sequence analysis; Structure analysis of Protein; Using biological softwares; Mining biological and bioinformatical data on Internet.

Animal Experiment

Resume of Gang Liu, PhD 2017

- 3 -

Experimental metastasis and spontaneous metastasis of cancer cells in host mice; In vivo imaging of tumor in host mice; genotyping of transgenic mice; preparation of tissue samples from host mice.

Journal Reviewer Experience

Working as active reviewer for a number of prestigious peer-reviewed journals that are internationally circulated, such as “Journal of Surgical Oncology”, “Tumor biology”, “Journal of Cancer Research and Clinical Oncology”, “Cancer Biomarkers”, “Journal of Experimental & Clinical Cancer Research”.

Working as Consulting Editor for “Gastrointestinal Cancer: Targets and Therapy”. Publications

1. AN McCracken, RJ McMonigle, J Tessier, R Fransson, MS Perryman, B Chen, A Keebaugh, E Selwan, SA Barr, SM Kim, SG Roy, G Liu, D Fallegger, L Sernissi, C Brandt, N Moitessier, AJ Snider, S Clare, M Müschen, A Huwiler, MT Kleinman, S Hanessian, AL Edinger. Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation. Leukemia. 2017 Mar;31(3):669-677.

2. Guenther GG*, Liu G equal contribution), Ramirez MU, McMonigle RJ, Kim SM, McCracken AN, Joo Y, Ushach I, Nguyen NL, Edinger AL. Loss of TSC2 confers resistance to ceramide and nutrient deprivation. Oncogene. 2014 Apr 3; 33(14):1776-87.

3. Lou S*, Liu G equal contribution), Shimada H, Yang X, He Q, Wu L. The lost intrinsic fragmentation of MAT1 protein during granulopoiesis promotes the growth and metastasis of leukemic myeloblasts. Stem Cells. 2013 Sep; 31(9):1942-53.

4. Gang Liu, Hai Zheng, Chunming Liu, Walden Ai. CTBPS Attenuate KLF4-Mediated Transcriptional Activation. Gastroenterology. 2009, 136(5), Supplement 1, A-265 5. Ying M, Liu G, Shimada H, Ding W, May WA, He Q, Adams GB, Wu L. Human osteosarcoma CD49f CD133 cells: impaired in osteogenic fate while gain of tumorigenicity. Oncogene. 2013 Sep 5; 32(36):4252-63.

6. Yunbo Jiang, Huihua Chen, Haiquan Jia, Yuanji Xu, Gang Liu, Yan Wang, Xiaohe Yang, Yinglin Lu. Adenovirus Ad-p53AIP1-mediated gene therapy and its regulation of p53-MDM2 interactions. Experimental and Therapeutic Medicine. 2010 (1): 363-368.

7. Gang Liu, Hai Zheng, Walden Ai. C-terminal binding proteins (CtBPs) attenuate KLF4-mediated transcriptional activation. FEBS Letter. 2009 Oct 6; 583(19): 3127-32. 8. Jinqiang Zhang*, Gang Liu* (*: equal contribution), Yuhong Meng, Huiyun Lin, Yinglin Lu. MAG-2 promotes invasion, mobility and adherence capability of lung cancer cells by MMP-2, CD44 and intracellular calcium in vitro. ONCOLOGY REPORTS. 2009, 21: 697-706 9. Hai Zheng, D. Mark Pritchard, Xiangdong Yang, Elaine Bennett, Gang Liu, Chunming Liu, Walden Ai. KLF4 gene expression is inhibited by the Notch signaling pathway that controls goblet cell differentiation in mouse GI tract. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2009, 296: G490–G498. 10. Jinqiang Zhang, Yuhong Meng, Huiyun Lin, Gang Liu, Yan Wang, Huihua Chen, Yuanji Xu, Zhiyan Du, Yinglin Lu. Promotion of MAG-1 on Metastasis of Lung Cancer Cells in vitro and Its Expression in Lung Cancer Tissue of 24 Cases. Chinese Journal of Lung Cancer. 2009 Feb 20; 12(2):93-99. 11. Jinqiang Zhang, Yuhong Meng, Gang Liu, Huihua Chen, Yan Wang, Yuanji Xu, Zhiyan Du, Yinglin Lu. The proliferation promoting effects of MAG-2 on human lung cancer cell PLA801. Chinese Journal of Lung Cancer. 2008 Aug 20; 11(4):513-518.

12. Yunbo Jiang, Yinglin Lu, Haiquan Jia, Yuanji Xu, Huihua Chen, Gang Liu, Yan Wang, Zhiyan Du. Anti-tumor effect of recombinant replication-defective adenovirus Ad-p53AIP1 and its related mechanism. Chinese Journal of Cancer Biotherapy. 2008, 15(6), 508-515.

13. Yuanji Xu, Tao Zhou, Zhiyan Du, Gang Liu, Weili Gong, Xiaodan Yu. A Novel Animal Model Established Using in Vivo Imaging to Monitor the Tumor Growth and Metastasis. ACTA LABORATORIUM ANIMALIS SCIENTIA SINICA . 2008, 16(1), 19-22.

14. Zhiyan Du, Yan Wang, Huihua Chen, Yuanji Xu, Dingyao Xu, Huiyun Lin, Gang Liu, Xiaogang Tan, Yinglin Lu. An Optimized Method for Packaging and Cloning Purification of Recombination Adenovirus. Letters in Biotechnology. 2006, 17(4), 586-589.

Resume of Gang Liu, PhD 2017

- 4 -

15. Gang Liu, Yuanji Xu, Yunbo Jiang, Haiquan Jia, Heping Pan, Zhiyan Du, Yinglin Lu. Polyclonal antibody specific to human tumor metastasis associated mag-2: preparation and identification. Bulletin of the Academy of Military Medical Sciences. 2007, 33 (3): 231-233. 16. Gang Liu, Yinglin Lu. Fatty acid synthase and neoplasms therapy. Chinese Journal of Cancer Prevention and Treatment. 2006, 13 (21): 1666-1669.

17. Y Jiang, X Wang, C Jin, X Chen, J Li, Z Wu, G Liu, S Li. Inhibitory effect of Periplaneta Americana extract on 3LL lung cancer in mice. Chinese Journal of Lung Cancer. 2006(9). 488-491. 18. Gang Liu, Yi Zhang, Yuanlin Liu, Jin He, Xiaoxia Jiang, Ning Mao. Ex vivo expansion of CD34+ cells from human umbilical cord blood by FL gene transfected bone marrow stromal cells. Journal of Experimental Hematology. 2003 Dec; 11(4): 341-344.

19. Jin He, Yi Zhang, Xiaoxia Jiang, Gang Liu, Yuanlin Liu, Helian Li, Ning Mao. Isolation and characterization of human placenta derived adherent cells and their hematopoietic growth factor expression. Chinese Journal of Hematology. 2003 Dec; 24(12): 652-654.

20. Yi Zhang, Jin He, Xiaoxia Jiang, Gang Liu, Yuanlin Liu, Pei-Shien Tang, Ning Mao. Human placenta derived adherent cells support in vitro expansion of umbilical cord blood CD34+ cells. Journal of Experimental Hematology. 2003 Dec; 11(6): 560-564.

21. Jin He, Yi Zhang, Xiaoxia Jiang, Gang Liu, Yuanlin Liu, Helian Li, Ning Mao. Effect of human bone marrow mesenchymal stem cell on cord blood T lymphocyte transformation. Journal of Experimental Hematology. 2003 Feb; 11(1): 11-14.

Conference Abstracts

1. Gang Liu, Jannett Nguyen, Aimee l. Edinger. Role of protein Phosphatase 2A in FRT720-induced Nutrient Transporter Protein Down-regulation. Keystone Symposia on Molecular and Cellular Biology (2013). 2. Garret Guenther, Gang Liu, Manuel Ramirez, Ryan McMonigle, and Aimee Edinger. Loss of TSC2 confers resistance to ceramide and nutrient deprivation. Keystone Symposia on Molecular and Cellular Biology (2013). 3. Yinglin Lu, Huiyun Lin, Xiaogang Tan, Jinqiang Zhang, Yuanji Xu, Huihua Chen, Yan Wang, Gang Liu, Zhiyan Du. Investigation of a novel metastasis associated gene mag-1. Clinical & Experimental Metastasis. 2007, 24(4): 260-261

4. Yinglin Lu, Huiyun Lin, Xiaogang Tan, Gang Liu, Huihua Chen, Yan Wang, Yuanji Xu, Zhiyan Du. Investigation of a novel metastasis associated gene mag-1. The 4th Chinese Conference on Oncology & 5th Cross-Strait Academic Conference on Oncology, 2006 Oct: 108. 5. Yinglin Lu, Xiaogang Tan, Huiyun Lin, Gang Liu, Huihua Chen, Yan Wang, Yuanji Xu, Zhiyan Du. Identification of Mag-1 function by RNA interference. The 4th Chinese Conference on Oncology & 5th Cross- Strait Academic Conference on Oncology. 2006 Oct: 109. References

1. Aimee Edinger, VMD/PhD

Assoc. Professor, Developmental and Cell Biology

University of California, Irvine

Irvine, CA 92697

Email:********@***.***

Tel: 949-***-****

2. Lingtao Wu, MD, PhD

Professor, the Children’s Hospital Los Angeles, University of Southern California 4650 Sunset Blvd., Los Angeles,

CA 90027, United States

Ph (Lab): 323-***-****

Email: ********@***.***

3. Saurabh GhoshRoy, PhD

EIS Consultant

Amgen, Thousand Oaks, California

Ph (cell):951-***-****

Email: ***************@*****.***

Contact this candidate