Xin Yang Ph.D.

( 650-***-**** * ad1bci@r.postjobfree.com þ Palo Alto, California

PROFESSIONAL SUMMARY:

My professional achievements reflect my decade years of unwavering scientific curiosity and passion for delving into the intricate workings of cancer, stem cell and translational medicine. My enriched experience involved hot topics of CRISPR, hematopoietic stem cells, iPSC, and humanized mouse models on immuno-oncology and gene/cell therapy. The complemented expertise I dedicated focus on cutting-edge omics studies and pathological strategies. There are four research projects I have leaded, including: RESEARCH PROJECT --- Leadership

1: Investigating the Pro-inflammatory Roles of Death Receptors in the Tumor Angiogenesis. 2: Employing CRISPR-induced Mutations in Human Cord Blood CD34+ Hematopoietic Stem Cells to Decode Human MLLr Leukemogenesis.

3: Unraveling the Epigenetics Control of the Evolving Metabolic Landscape in MLLr Leukemic Stem Cells. 4: Pioneering Humanized PBMC/HSC Mouse Models for Immuno-oncology, Infectious diseases, and Metabolic Disorders.

CLINICAL TRIAL (Pre-IND) --- Participate

I participated Hemophilia A gene therapy pre-IND project and experienced medical writing on Investigator Protocol both in English and Chinese. And I played a role as a medical liaison and coordination between industry sponsor and clinical trial sites.

EXPERTISE HIGHLIGHTS

• Inflammatory pathways in tumor angiogenesis interaction.

• CRISPR/Cas9 gene editing in cancer cell lines, hematopoietic stem cells and iPSCs.

• Hematopoietic stem cell expansion and regenerative strategies.

• Oncogenic mutations in hematopoietic clonal evolution.

• Characterization of global gene expression in human leukemic stem cells.

• Metabolic factors in hematopoiesis and leukemic transformation.

• PBMC/HSC human immune system reconstitution in NSG mice.

• iPSC-derived CD34+ cells and hematopoietic stem cells differentiation.

• Tissue/cell bank establishment and management.

• Animal management and operation.

• Coordinate clinical trial for gene therapy and medical writing. RESUME CONFIDENTIAL

EDUCATION

Stanford University 2021

Postdoctoral Researcher

Chinese Academy of Medical Sciences / Peking Union Medical College / Tsinghua University 2013 Doctor of Philosophy

Shanxi University / Institute of Microbiology Chinese Academy of Science 2010 Master of Science

Shanxi Agricultural University 2006

Bachelor of Science

PROFESSIONAL EXPERIENCE

Applied StemCell, Inc. (Cell & Animal Production) Milpitas, CA Scientist 2023 –

• Product development of PBMC/GvHD humanized NSG mice, advancing pre-clinical disease model for T cells response.

• Established CD34+ humanized mice for human immune system reconstitution, contributing to the generation of innovative pre- clinical disease models and promoting further understanding of disease progression and treatment efficacy.

• Research and developed on validation assays for hiPSC-derived CD34+ hematopoietic stem and progenitor cells in vitro and in vivo.

• Collaborated with a multidisciplinary team to pioneer novel approaches in stem cell research and applications.

• Employed cutting-edge techniques in stem cell manipulation and molecular biology to create reliable and accurate humanized mouse models, enhancing the validity of pre-clinical studies.

• Assisted in the preparation and presentation of research findings for both internal and external stakeholders, showcasing the impact of the developed humanized disease models on the understanding of disease mechanisms.

• Industry Standard Operation Procedure (SOP) generation and revision.

• Medical writing for protocol, IRB documents on preparing documents for pre-IND filing (>5yrs).

• Medical liaison between sponsor and clinical sites. Stanford University (Pathology Department) Palo Alto, CA Basic Life Research Scientist 2021 – 2022

• Employed CRISPR techniques and whole transcriptome analysis in CD34+ hematopoietic stem cells and transformed CD34+ hematopoietic stem cells for exploring critical factors involving in hematopoietic stem cells exhaustion and lineage markers identification.

• Investigated on novel drug targets for human leukemic stem cells, contributing to the development of potentially therapies.

• Tissue/cell bank management and inventory update.

• Authored and co-authored multiple peer-reviewed publications, disseminating research findings to the scientific community and advancing the collective understanding of leukemic stem cell biology and treatment options. Stanford University (Pathology Department) Palo Alto, CA Postdoctoral Research Fellow 2016 – 2021

• Utilized cutting-edge CRISPR/Cas9 technologies to create precision oncogene mutations, advancing the understanding of oncogene- driven human leukemia models in vivo and in vitro.

• Conducted in-depth investigations into the mechanisms of leukemogenesis, uncovering novel insights into the development and progression of leukemia.

• Established humanized leukemia cell bank from normal CD34+ cells to malignant transformed cell lines, including MLL-ENL, MLL- AF9, MLL-AF4 immortalized cell lines (approximately 2000 lines).

• Established humanized leukemia tissue bank for long-term transplantation. The tissue bank included bone Marrow, spleen, spine, lymphoid nodes, thymus (approximately 1000 vials).

• Authored and co-authored multiple peer-reviewed publications, showcasing the impact of CRISPR/Cas9 technologies on leukemia research and highlighting innovative approaches to understanding and treating the disease. RESUME CONFIDENTIAL

Second Hospital of Shanxi Medical University (Obstetrics & Gynecology Department) China Lecturer 2014 – 2016

• Spearheaded research on cervical cancer within the Gynecology and Obstetrics department at the Second Hospital of Shanxi Medical University, contributing to advancements in the understanding and treatment of the disease.

• Collaborated closely with physicians to design and conduct clinical trials, ensuring the seamless integration of research findings into clinical practice for improved patient outcomes.

• Educated and mentored M.D. students in performing biomedical research, fostering the next generation of skilled medical professionals with a strong foundation in research methodologies and critical thinking.

• Developed and delivered engaging lectures on the latest developments in cervical cancer research, promoting a culture of continuous learning and keeping students and colleagues up to date with cutting-edge knowledge.

• Participated to establish cervical neoplasia tissue bank from cervical cancer patients and pre-screened CIN patients (approximately 40,000). Tissue bank management.

• Authored and co-authored multiple research papers on cervical cancer, disseminating important findings to the wider scientific and medical communities and advancing the collective understanding of the disease. Tsinghua University (Immunology) China

Research Assistant 2013 – 2014

• Conducted in-depth research on the NOTCH signaling pathway, contributing to a better understanding of its role in various biological processes and potential therapeutic applications.

• Mentored and educated graduate students on performing experiments, fostering a collaborative and supportive research environment while helping to develop the next generation of skilled researchers.

• Employed state-of-the-art molecular biology techniques and laboratory equipment to generate accurate and reliable experimental data, furthering the advancement of knowledge in the field. EXPERIMENTAL SKILLS

Molecular Design & Genetic Engineering & Data Analysis:

• CRISPR design, CRISPR platform selection, optimization, and perform gene editing related experiments

• Precision gene knockouts, point mutations, insertions

• Molecular cloning, gene overexpression, gene knockdown

• NGS analysis for gene editing efficiency, mutation rates, mutation drift analysis

• Functional genes analysis, qPCR, ELISA, Western Blot, Cellular & Cell Models & Analysis:

• Mammalian cell line culture and transfection

• Human CD34+ hematopoietic stem cell (HSC) culture (2D/3D), differentiation (3D), and transfection (2D)

• Human CD34+ HSC malignant transformation (AML or B-ALL both ex vitro and in vivo)

• Identification and characterization of HSC, T, B, NK cells, monocytes, erythroid cells

• Human iPSCs culture and differentiate to HSC, T, B, NK, monocytes, erythroid cells

• Cells-based analysis: Flow Cytometry (FACS), colony forming unit assays (CFU), cells morphologies, mutation caused growth rate, cell death, migration, colony growth, trans-well assays and tailored analyses as needed. Animal Handling & Models & Analysis:

• Mice husbandry and breeding

• CDX (Cell line derived xenografted), PDX (Patient derived xenografted) and humanized mouse models with i.v/i.p/subcutaneous injection

• Mice phenotype analysis: survival, tumor grow analysis, GvHD analysis

• Tissue-based analysis: tissue collection (peripheral blood /bone marrow / spleen / lymph nodes / spine collection and analysis), tumor blood vesicular analysis, blood smear, HE/IHC, FACS analysis, pathological examination as needed

• Pre-clinical disease models (humanized PBMC, CD34+ NSG models, humanized B-ALL/AML leukemia models) Bioinformatics:

• CRISPResso2 platform for gene editing analysis

• Partek Flow platform for RNA-seq analysis

• R2 Genomics Analysis and Visualization platform

RESUME CONFIDENTIAL

Additional Skills:

• Experienced in medical writing with bilingual proficiency in English and Chinese

• Collaborative experience with academic and industry teams

• Familiar with FDA regulations

• Medical writing for protocol of pre-clinical trials documents filing (US and Chinese FDA) PUBLICATIONS

• Xiao Yu, Weihong Zhao, Xin Yang, Zhilian Wang, Min Hao*. miR-375 affects the proliferation, invasion and apoptosis of HPV16-positive human cervical cancer cells by targeting IGF-1R. International Journal of Gynecological Cancer, 2016,26(5):851-8

• Yonghong Wang, Yanru Jia, Xin Yang, Bin Liang, Hongjuan Gao, Taotao Yang. A potential role of Baicalin to inhibit apoptosis and protect against acute liver and kidney injury in rat preeclampsia model

• Xin Yang, Bianhua Shi, Lingxue Li, Zhenbiao Xu, Yehua Ge, Juan Shi*, Yanxin Liu*, Dexian Zheng. Death Receptor 6 (DR6) is Required for Mouse B16 Tumor Angiogenesis via NF-κB, P38 MAPK and STAT3 Pathways. Oncogenesis, 2016(5), e206

• Xin Yang, Xiangrong Zhang, Mingju Zhang, Wenchao Guo, Yingchuan Tian, Qizhong Xia and Jiahe Wu*. Transgenic potato overexpressing the Amaranthus caudatus agglutinin gene to confer aphid resistance. Crop Science, 2011,51(5): 2119-2124

• Min Hao*, Weihong Zhao, Lili Zhang, Honghong Wang, Xin Yang. Low folate levels are associated with methylation-mediated transcriptional repression of miR-203 and miR-375 during cervical carcinogenesis. Oncology letters, 2016, 11: 3863-3869

• Zhenbiao Xu, Lianmei Zhao, Xin Yang, Sisi Ma, Yehua Ge, Yanxin Liu, Shilian Liu, Juan Shi* and Dexian Zheng*. Mmu-miR-125b overexpression suppresses NO production in activated macrophages by targeting eEF2K and CCNA2. BMC Cancer, (16): 252

• Zhao WH, Hao M, Cheng XT, Yang X, Wang ZL, Cheng KY, Liu FL, Bai YX. c-myc Gene Copy Number Variation in Cervical Exfoliated Cells Detected on Fluorescence in situ Hybridization for Cervical Cancer Screening. Gynecol Obstet Invest. 2016 Jan 26

• Feng Pan, Masayuki Iwasaki, Wenqi Wu, Yanan Jiang, Xin Yang, Li Zhu, Zhigang Zhao, Michael L Cleary*. Enhancer remodeling drives MLL oncogene-dependent transcriptional dysregulation in leukemia stem cells. Blood Adv, Jan 27, 2023

• Yu Nie, Jiangjiao Li, Aihua Liang, Xin Yang, Zhiyun Zhang, Wei Wang*. EoRab43 is an atypical Rab gene in Euplotes octocarinatus. Acta Zoological Sinica, 2008,54(1):128-135. (Academic Journal in Chinese)

• Xin Yang, Aihua Liang, Jiahe Wu*. Progression of transgenic insect-resistant potato. Journal of biology, 2010, 27(155):66-68.

(Academic Journal in Chinese)

• Xin Yang, Aihua Liang, Xiaoli Luo, Jiahe Wu*. Cloning and characterization of mannose-6-phosphate isomerase gene manA/pmi from Escherichia coli. Acta Agriculturae Boreali-Sinica, 2011, 26(2):107-110. (Academic Journal in Chinese)

• Wei Wang, Haixia Luo, Jingjing Chang, Xin Yang, Xiu Zhang, Qingmei Zhang, Yuanxing Li, Yueyang Zhao, Jianbing Liu, Binbin Zou & Min Hao*. Circular RNA circ0001955 promotes cervical cancer tumorigenesis and metastasis via the miR-188-3p/NCAPG2 axis. Journal of Translational Medicine, 29 May, 2023, 21.

• Feng Pan, Jolanda Sarno, Johan Jeong, Xin Yang, Astraea Jager, Tanja A Gruber, Kara L Davis, Michael L Cleary*. Genome editing- induced t (4;11) chromosomal translocation model B cell precursor acute lymphoblastic leukemia with KMT2A-AFF1 fusion. The Journal of Clinical Investigation, 2023.

ABSTRACT

• Xin Yang, Xu ZB, Shi J, Liu YX, Zheng DX. Functions of death receptor6 (DR6) in tumor microenvironment. The 2nd Hsien Wu and Ray Wu Symposia “Proteins, Genes, and Diseases”, 2012, Beijing, China

• Xu ZB, Xin Yang, Ma SS, Zhao LM, Liu YX, Shi J, Zheng DX. MiRNA-1 overexpression inhibits nitric oxide production from macrophage. The 2nd Hsien Wu and Ray Wu Symposia “Proteins, Genes, and Diseases”, 2012, Beijing, China

• Xin Yang, Li Zhu, Feng Pan, Kara Davis, Michael Cleary. Deciphering metabolic evolution of human MLLr leukemic stem cells. Pathology Retreat, Pathology Department, 2022, Stanford University RESUME CONFIDENTIAL

MANUSCRIPTS (2023 SUBMISSION)

• The role of ENL YEATS domain in orchestrating OSBPL1A and OSBPL5 expression for MLLr leukemic stem cells. (Research Article)

• NRAS point mutations transiently expedite clonal evolution in human MLLr leukemic stem cells (Research Letter)

• T cell function in humanized PBMC/HSC mouse models. (Book Chapter) Clinical Research Associate (CRA)

CERTIFICATIONS

Certificate for The Informed Consent Process

Certificate for IRB Reporting-Unanticipated Problems, Non-Compliance, and other Reportable Events Certificate for HIPAA/Protecting Patient Privacy

Certificate for Overview of Clinical Research Sources at Stanford University Certificate for Bloodborne Pathogens

Certificate for General Safety

Certificate for Injury Prevention (IIPP), and Emergency Preparedness Certificate for Biosafety

Certificate for Chemical Safety for Laboratories

Certificate for Laboratory Animal Care &Use

Certificate for Animal Facility Training Certificate for Working at Animal Biosafety Level

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