Gene Therapy Associate Director

Yildirim Dogan, Ph.D.

Cell phone +1-917-***-****

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

Linkedin https://www.linkedin.com/in/yildirim-dogan

Summary

●Expertise in developing clinical gene therapy vectors.

●Expertise in industrial bioanalytical assay development for preclinical and clinical needs.

●Expertise in developing and executing IND-enabling proof-of-concept in-vivo lentiviral gene therapy studies.

●Expertise in human and mouse hematopoietic stem cell and tissue engineering.

●Expertise in developing mRNA based VLP & non-viral gene transfer tools.

Professional Experience

Feb 2022 to present Associate Director in Transgene Biology at Moderna Therapeutics, Genomics, Cambridge MA

•Leading a small group of scientists

•Leading the design of mRNA and DNA constructs for novel gene transfer tools

•Leading the development of bioanalytical assays to detect nucleotide constructs in transfected cells by QPCR, ddPCR, RT-QPCR, IF, confocal microscopy & nuclease protection assay

•Leading the development of mRNA-based virus like particles for non-viral gene transfer

•Leading the development of processes to establish non-dividing cell lines by inducible cell cycle arrest

Jan 2021 to Jan 2022 Associate Director in clinical & preclinical Gene Therapy for

Lysosomal Storage diseases. AVROBIO, Cambridge, MA

•Successfully directed a preclinical proof of biology study in our R&D team to test the efficacy of new experimental drug products in one of our lead disease programs.

•Collaboratively, I developed the clinical vector and the key bioanalytical assay for our Hunter program.

•Supported writing regulatory drug applications

•Managing a direct report.

•Developed mass spectrometric glycolipid quantification methods with a CRO for precise biodistribution and drug efficacy analyses in preclinical and clinical applications.

•Supported our CMC department in various clinical assay development efforts.

•Wrote scientific manuscripts published in peer reviewed journals.

Jan 2020 to Jan 2021 Senior Scientist in clinical & preclinical gene therapy drug

development for rare diseases. AVROBIO, Cambridge, MA

•Developed various clinical assays for AVROBIO's lead program.

•Shown improved efficacies of novel lentiviral vectors in human CD34+ cells to advance them to preclinical testing.

•Managed direct reports.

•Acting gene therapy specialist of AVROBIO.

June 2018 to Jan 2020 Scientist II in preclinical gene therapy drug development for

rare diseases. AVROBIO, Cambridge, MA

•Successfully supervised a proof-of-biology study for a new preclinical gene therapy program at a CRO.

•Successfully supervised an IND-enabling gene therapy proof-of-concept study at a CRO for the AVROBIO's Pompe disease pipeline.

•Successfully supervised and completed a gene therapy vector comparison study at a CRO to advance vectors for the Pompe preclinical lysosomal storage disease pipeline.

•Successfully supervised and completed various gene therapy pilot studies at CROs for multiple preclinical lysosomal storage disease pipelines.

•Successfully trained CROs for procedures in lentiviral gene therapy.

•Developed and wrote study protocols for CROs for testing drug products of various AVROBIO preclinical lysosomal storage disease pipelines.

•Managed direct reports.

•Developed various in vivo study protocols and discussed with various stake holders to advance best protocols.

•Analyzed raw data of various studies and reported to various stake holders.

•Successfully screened in vitro lentiviral gene therapy vectors and advanced top performing vectors for an in-vivo proof-of-biology testing.

•Designed, cloned and tested novel lentiviral gene therapy vectors to improve expression of drug products for AVROBIOs clinical lead program.

•Developed various in-house SOPs for method transfer to CROs.

•Validated an automated (ROBOSEP) hematopoietic stem cell (HSC) isolation procedure.

•Developed and wrote SOPs for lentiviral gene transfer protocols for ex-vivo gene transfer into hematopoietic stem cell.

•Developed and wrote SOPs for vector copy number assessment of therapeutic lentiviral vectors.

•Developed a real-time-quantitative-pcr assay with a CRO to assess biodistribution of gene therapy drug products based on absolute mRNA quantification.

•Developed lentiviral vector production procedures for method transfer to manufacturers.

•Acting gene therapy specialist of various AVROBIO pipeline programs.

•Acting principal investigator of AVROBIO institutional biosafety committee (IBC).

Jan. 2018- June 2018 R&D Scientist I in preclinical gene therapy drug development

for rare diseases. AVROBIO, Cambridge, MA

•Developed in-vitro cell uptake assays for screening efficacies of lysosomal proteins in LSD knock out cell lines.

•Generated stable cell lines for in-vitro production of lysosomal protein drugs for FABRY disease.

•Generated and validated novel human knock-out cell lines for in vitro modeling of FABRY disease by Crispr/Cas9.

•Genetically engineered augmented lysosomal genes.

•Developed enzyme activity assays for bioanalytical testing of drug products.

•Reviewed and coordinated contracts between AVROBIO and various vendors and CROs.

•Reviewed, purchased and coordinated the setup of various scientific instruments for AVROBIO R&D labs.

2011 – Oct. 2016 Postdoctoral Research Fellow, postdoctoral Research Associate & Senior Research Scientist in ESC, iPSC Research and Epigenetics. Memorial Sloan Kettering Cancer Center, New York

●Developed a novel Chromatin Immunoprecipitation technique by CrispR/Cas9-mediated knock-in of a fluorescence & biotin-epitope tag to an endogenous ESC-specific transcription factor and validated by Next Generation Sequencing.

●Developed and functionally validated CrispR knock-in of genetic reporter in ES & iPSCs.

●Developed assays for testing drug-induced DNA damage response, cell stress and metabolic state of cells.

●Analyzed histone modification by histone acid extraction and Chip-Sequencing.

●Tested iPSC glycolysis & oxygen consumption by the Seahorse XF96 fluxanalyzer.

●Derived tumor cell lines from patient derived tumors.

●Generation of induced pluripotent stem cells by somatic cell reprogramming.

●Developed strategies to analyze tumorigenicity of aged iPSC in mouse in-vivo models.

●Developed bioluminescence marker for in-vivo cancer cell tracing.

●Analyzed DMRs by DNA bisulfite sequencing.

2008 – 2011 Postdoctoral Research Fellow in Leukemia Research Memorial Sloan Kettering Cancer Center, New York

●Developed lentiviral plasmid tools for modeling leukemia in human cord blood hematopoietic stem cells. Unveiled an oncogenic transport mechanism in a cell culture model by utilizing lentivirus Rev nuclear-cytoplasmic shuttling.

●Visualized nanotubes in mesothelioma by genetic fluorescence reporter.

●Assisted in modeling T-cell mediated GVHD suppression & anti-tumor activity.

Education

2008 Doctor of Philosophy in Biology Leibniz University Hannover, Germany

●Ph.D. Thesis Title: Designing bi-functional retroviral vectors for investigating the pathogenesis of myeloid diseases and for evaluation of therapeutic targets. Department of Experimental Hematology at Medical School Hannover

●Developed a mouse leukemia model by transplantation of ex-vivo modified syngeneic hematopoietic stem cells.

2004 Masters in Biology

Leibniz University Hannover, Germany

●Major in Cell and Developmental Biology. Minor in Immunology & Genetics.

●Master Thesis Title: Stable RNA-Interference in hematopoietic cells.

Certificates

2016-2017 Python for Everybody, a 5-course specialization by University of Michigan

on Coursera

●Programming for Everybody (Getting Started with Python).

●Python Data Structure.

●Using Python to Access Web Data.

●Using Databases with Python.

●Capstone: Retrieving, Processing, and Visualizing Data with Python.

2003 FELASA Category C-persons responsible for directing animal experiments

Skills

●Retroviral vector development, design and optimization

●Virus like particle design

●Generation of RNA & mRNA molecules by In vitro transcription (IVT)

●mRNA design, including UTRs, Introns, ORFs and Kozak

●RNA immunoprecipitation

●Click chemistry enabled nucleotide detection

●MS2 phage technology

●Generation of virus like particles

●Bioanalytical assay development.

●CrispR/Cas9 mediated genome editing, RNAi and tissue engineering.

●Chromatin immunoprecipitation and Chip-Sequencing, epigenetic characterization and histone modifications.

●Generation of induced pluripotent stem cell (iPSC), iPSC and embryonic stem cell (ESC) culture and other cell cultures and cell line development techniques.

●Flow cytometry, fluorescence and confocal microscopy.

●RT-QPCR and QPCR, PCR

●Molecular Cloning, retrovirus production and lentiviral transductions.

●Bioanalytical assays with microplate reader

●Protein blotting, JESS and conventional western blotting.

●Primary cell and cell line culturing

●Working knowledge of bioinformatics including data processing and visualization.

●Knowledgeable in GraphPad Prism, IGV, SnapGene, FlowJo, ImageJ.

●Proficient in Microsoft Office Suite (Word, Excel, PowerPoint), Mac OS, Windows OS.

●Native language English, German and Turkish.

Managerial training

●Leading for Innovation- Moderna University, Manager Academy, 2023

●Given High Impact Feedback -Moderna University, Manager Academy, 2023

●BetterUp Coaching, 2023-present

Animal Experimentation Skills

●Autologous transplantation of lentivirally gene modified hematopoietic stem cells into conditioned knock out mice.

●Testing teratoma formation of sub-cutaneous injected pluripotent stem cells into immune-

suppressed mice.

●Tracking bioluminescence-labeled (pUltra-Chili-Luc) cancer cells in immune-suppressed mice by retro-orbital luciferin injection.

●Testing engraftment potential of GFP-labeled iPSC and ESC-derived hematopoietic stem cells into immune-suppressed NOD-SCID IL2g mice.

●Modeling leukemia with genetically modified human Cord blood derived hematopoietic stem cells by transplantation into immune-suppressed NOD-SCID IL2g mice.

●Mouse intravenous, intraperitoneal & retroorbital injections.

●Mouse breeding and genotyping of genetically modified mice.

●Animal imaging including IVIS in vivo imaging system.

Scientific Tools

pUltra 3rd generation Lentiviral vector for multi-cistronic expression of EGFP and two genes of interest. Among the most popular Addgene lentiviral transfer plasmids.

pUltra-hot 3rd generation Lentiviral vector for multi-cistronic expression of mCherry and two genes of interest. Among the most popular Addgene lentiviral transfer plasmids.

Complete List: http://www.addgene.org/search/advanced/?q=pultra

Patent

Method to reduce oncogenic potential of induced pluripotent stem cells from aged donors. Memorial Sloan Kettering Cancer Center, team assignee. World patent WO 2016/057574 A1. 2016 Apr 14.

Scientific Conference Presentations

Long-term hematopoietic stem cell gene therapy corrects neuromuscular manifestations in preclinical study of Pompe mice. NP van Til, Y Dogan, C Barese, Z Unnisa, S Guda, R Schindler, J Yoon, et al. Mol Cancer Ther August 1 2021 (20) (8) 1388-1399

Hematopoietic Stem Cell Gene Therapy Corrects Neuromuscular Manifestations in Preclinical Study of Pompe Mice. NP van Til, Y Dogan, C Barese, Z Unnisa, S Guda, R Schindler, J Yoon, et al. MOLECULAR THERAPY. Vol. 28. No. 4. CELL PRESS, 2020.

Bibliography

Screening chimeric GAA variants in preclinical study results in hematopoietic stem cell gene therapy candidate vectors for Pompe disease. Dogan Y, Barese CN, Schindler JW, Yoon JK, Unnisa Z, Guda S, Jacobs ME, Oborski C, Maiwald T, Clarke DL, Schambach A, Pfeifer R, Harper C, Mason C, van Til NP. Mol Ther Methods Clin Dev. 2022 Nov 3;27:464-487. PMID: 36419467; PMCID: PMC9676529.

High-throughput analysis of hematopoietic stem cell engraftment after intravenous and intracerebroventricular dosing. Plasschaert RN, DeAndrade MP, Hull F, Nguyen Q, Peterson T, Yan A, Loperfido M, Baricordi C, Barbarossa L, Yoon JK, Dogan Y, Unnisa Z, Schindler JW, van Til NP, Biasco L, Mason C. Mol Ther. 2022 Oct 5;30(10):3209-3225. Epub 2022 May 25. PMID: 35614857; PMCID: PMC9552809.

CSF-1/CSF-1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-Cell Infiltration in the Sarcoma Microenvironment. Fujiwara T, Yakoub MA, Chandler A, Christ AB, Yang G, Ouerfelli O, Rajasekhar VK, Yoshida A, Kondo H, Hata T, Tazawa H, Dogan Y, Moore MAS, Fujiwara T, Ozaki T, Purdue E, Healey JH. Mol Cancer Ther. 2021 Jun 4. PMID: 34088832.

Multifaceted regulation of somatic cell reprogramming by mRNA translational control. Tahmasebi S, Alain T, Rajasekhar VK, Zhang JP, Prager-Khoutorsky M, Khoutorsky A, Dogan Y, et. al. Cell Stem Cell. 2014; 14(5):606-16.

Crizotinib, a c-Met inhibitor, prevents metastasis in a metastatic uveal melanoma model.

Surriga O, Rajasekhar VK, Ambrosini G, Dogan Y, Huang R, Schwartz GK.

Molecular Cancer Therapeutics. 2013; 12(12):2817-26.

Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity.

Ghosh A, Dogan Y, Moroz M, et al. The Journal of clinical investigation. 2013; 123(6):2654- 62.

PLZF confers effector functions to donor T cells that preserve graft-versus-tumor effects while attenuating GVHD. Ghosh A, Holland AM, Dogan Y, et al. Cancer research. 2013; 73(15):4687-96.

Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma. Lou E, Fujisawa S, Morozov A, Barlas A, Romin Y, Dogan Y, Gholami S, Moreira AL, et. al. PloS one. 2012; 7(3):e33093.

Benign mesenchymal stromal cells in human sarcomas.

Morozov A, Downey RJ, Healey J, Moreira AL, Lou E, Franceschino A, Dogan Y, et al.

Clinical cancer research. 2010; 16(23):5630-40.

Quantification of transforming capacity and cooperation of defined genetic alterations in myeloid malignancies.

Dogan Y, Ganser A, Scherr M, Eder M. Experimental hematology. 2010; 38(1):11-9.

Citations

https://scholar.google.com/citations?user=0jn-pSIAAAAJ&hl=en

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