Cancer Research

Resume

Fazal Shirazi, PhD

E-mail: *****.*******@*****.***

Phone number: 713-***-****

Ph.D. In Biotechnology with 14+ years of professional translational research experience in infectious disease/hematology/oncology in academia

Experience in assay development: qPCR-based assays, cytotoxicity assays (flow cytometry based, IncuCyte)

Extensive knowledge of cancer biology and translational biomarker development

Experience in creating different in vivo mouse model system to study tumor pathogenesis

Deep understanding in translational research with emphasis in multiple myeloma, Tumor Immunology, Immunotherapy, Epigenetics, infectious disease and drug screening.

Validation of efficacy of the newly discovered drug

Good knowledge bio statistical and bioinformatics methods/tools

Experience in writing standard operating procedures, scientific report, manuscripts.

Design, mentor and monitor of execution research projects, ability to work independently and in a dynamic team environment

Strong work ethic, ability to manage time and meet project timelines, and ability to independently identify problems and develop solutions

Very good interpersonal skills and strong communication skills

Techniques and skills:

Molecular Biology: Gene manipulation (CRISPR/Cas9) and molecular cloning, real time PCR, quantitative polymerase chain reaction (qPCR/QRTPCR), RNA and DNA isolation, quantification and analysis, shRNA, miRNA, siRNA, Sequence analysis including phylogenetics, and method development and optimization.

Cell manipulation: Cancer cell culture both in 2D and 3D format, primary cell culture, co-culture, microbial cultures, retro- and lentiviral transduction, Isolation, identification and characterization of microorganisms, cell isolation and culture, morphological assessment, cell proliferation, functional differentiation

Biochemistry and biophysics: Intracellular protein purification techniques, analytical techniques such as native and SDS-poly-acrylamide gel electrophoresis, capillary electrophoresis, immunohistochemistry, confocal and fluorescence microscopy, western blot, Luminex Assay, MTT cell proliferation assay, flow cytometry, FACS, IncuCyte assays, cytotoxicity, detection of marker expression, cellular and biochemical assays, ELISA, molecular devices plate reader (fluorescence, luminescence and absorbance), High Throughput Screening and identify, characterize, and evaluate novel targets for the treatment of infectious diseases etc.

Animal Handling: Maintenance, handling and development of different in vivo cancer mouse model system (systemic, subcutaneous, Orthotropic, PDX etc), extraction of bone marrow from mice, good knowledge of statistics and bioinformatics tools.

Proficiency in MS word, Power Point, excel to perform data acquisition, analysis and prepare reports.

Research Experience:

Research Instructor: Department of Lymphoma/Myeloma, UT M.D. Anderson Cancer Center, University of Texas, USA reporting directly to Chair of department, Houston, TX (April 2017 - Present)

Development of New therapeutic strategies for the relapsed Multiple Myeloma and identification

Validation of new myeloma drug targets.

Identification of drug targets for therapeutic vulnerability in high risk myeloma patients e.g. 17p deletion.

Designed and conducted independent research projects to investigate the role of RAS/RAF mutations in the Multiple Myeloma and associated Unfolded protein response (UPR/ER stress pathway) & Ubiquitin proteasome pathway.

Successfully executed hematological malignancy studies and monitored tumor progression using CT-scan, analyze tumor lesions and performed ex-vivo analysis by IHC, IF, WB, and FACS also expert in high-throughput RNA-Seq and ChIP-Seq analysis and further delineated underlying molecular mechanisms using cell-based models.

Involved in screening and testing small molecule inhibitors in hematological cancer and other infectious disease cell lines.

Discovery of bio markers and lead characterization of monoclonal antibody drug candidates relevant for targeted therapy using available databases and validating therapeutic bio markers in vitro and in vivo

Handling Translation research projects, data analysis, and training Postdocs for designing, publishing research articles, managing IRB protocols and writing grant proposals.

Developed q-PCR based assay for integrated copy number quantification, for detection Multiple Myeloma biomarkers in bone marrow and primary patient samples

Extensively characterized Multiple Myeloma cells phenotype and function using multi-parameter flow cytometry, ELISA and IncuCyte.

Post-Doctoral Fellow: Department of Lymphoma/Myeloma UT MD Anderson Cancer Centre, Houston, TX (2014 - 2017)

Designed and conducted independent research projects to investigate the role of the RAS and RAF mutations in the multiple myeloma development and tumorigenesis using cell lines and mouse models to understand role MAPK signaling and ER stress signaling pathway and Proteasome Load and Capacity in cancer progression. Also Understanding role of p53 deletion in MM by creating p53 CRISPR KO cell lines invitro and in vivo mouse models.

Expertise in development of cellular models using the ectopic expression (luciferase, GFP, RFP stable lines), gene knockdown (RNAi), gene editing (CRISPR/Cas9), and Site-directed mutagenesis for functional and mechanistic studies.

Experience in analyzing and interpreting RNAseq and ChIPSeq data.

Extensive experience in development and evaluation of xenograft mouse models for target validation, tumor monitoring by imaging and ex-vivo analysis.

Post-Doctoral Fellow: Infectious Disease, UT MD Anderson Cancer Center, Houston, TX

(2012 - 2014)

Investigation of fungal pathogenesis, apoptosis, and biofilm formation in Murine, Drosophila and Zebrafish models in the setting of obesity and diabetes

Characterized biochemical and molecular apoptotic pathway involved in fungal pathogenesis and apoptosis in cancer and immunocompromised patients

Senior Research Fellow: Dept. of Biochemical Sciences, National Chemical Laboratory, Pune, India (2007 - 2010)

Developed and screened novel fungicides and study of their efficacy in fungal infections. Research Assistant: Dept. of Biochemical Sciences, National Chemical Laboratory, Pune, India (2004- 2007)

Screened >50000 organic and microbial compounds against various targets specifically present and important in survival of pathogenic fungus. Out of 50000 thousand four leads were identified and were patented and licensed to Rallis India Limited.

Education:

PhD in Biotechnology from National Chemical Laboratory and University of Pune, India.

M.S. in Biotechnology from Guru Ghasidas University, Bilaspur, India.

Achievements:

Oral presentations:

1. The Anti-Tumor effect of the Ubiquitin-Activating Enzyme (UAE) inhibitor TAK-243 on pre-clinical Models of Multiple Myeloma. ASH 2016, San Diego, CA

2. A novel B-cell maturation antigen (BCMA)-targeted antibody conjugated to a amanitin, is active against myeloma with preferential efficacy against pre-clinical models of deletion 17P. ASH 2018, San Diego, CA

3. Activating KRAS, NRAS and BRAF mutants enhance proteasome capacity and reduce endoplasmic reticulum stress in multiple myeloma, thereby promoting plasma cell survival and proteasome inhibitor resistance. ASH 2018, San Diego, CA

4. Diet modification and metformin have a beneficial effect in a fly model of obesity and disseminated mucormycosis. Center for Energy Balance in Cancer Prevention and Survivorship, MD Anderson Cancer Center, Houston TX

5. Interscience Conference on Antimicrobial Agents and Chemotherapy held at San Diego, California, 2015

1. Do statins impact the biology of Rhizopus oryzae: In vitro and in vivo investigations”

2. “Pseudomonas aeruginosa strains isolated from cystic fibrosis patients strongly induce apoptosis and inhibition of Aspergillus fumigatus biofilm”.

6. Interscience Conference on Antimicrobial Agents and Chemotherapy held at Washington DC, 2014 “Iron starvation induces apoptosis in Rhizopus oryzae in vitro”.

Awards and Honors

DAAD (German academic exchange program) Sandwich Fellowship (2007-2008).

Amgen Best Oral Presentation Award in Trainee Research Day in MD Anderson Cancer Center, Houston (2013)

ASM Student and Post-Doctoral Fellows Travel Grant for ICAAC, 2013

Best Poster Award in Third Infection in Cancer Symposium in MD Anderson Cancer Center, Houston (2013)

Basic Science Category Poster Award finalist in MD Anderson Cancer Center, Div. of Internal Medicine Retreat, Houston (2014)

Relevant publications:

https://scholar.google.com/citations?user=JF5wC0gAAAAJ&hl=en:

1.Ni H*, Shirazi F*, Baladandayuthapani V, Lin H, Kuiatse I, Wang H, et al. Targeting Myddosome Signaling in Waldenström's Macroglobulinemia with the Interleukin-1 Receptor-associated Kinase 1/4 Inhibitor R191. Clin Cancer Res.

2.Zhang X*, Lee HC*, Shirazi F*, Baladandayuthapani V, Lin H, Kuiatse I, et al. Protein Targeting Chimeric Molecules Specific for Bromodomain and Extra-terminal Motif Family Proteins are Active against Pre-Clinical Models of Multiple Myeloma. Leukemia 32(10):2224–2239, 10/2018.

3.Jain N, Sehgal L, Havranek O, Singh R.K., Khashab T, Shirazi F, et al. Simultaneous inhibition of PI3K-p110β and PI3K-p110δ for sensitization of ibrutinib-resistant diffuse large B cell lymphoma. Haematologica. (Submitted).

4.Zhang J*, Shirazi F*, Singh RK, Kuiatse I, Wang H, Lee HC, et al. Ubiquitin-activating Enzyme Inhibition Induces an Unfolded Protein Response and Overcomes Drug Resistance in Myeloma. Blood. (doi: https://doi.org/10.1182/blood-201*-**-******).

5.Wang H*, Shirazi F*, Baljevic M, Wang X, Kuiatse I, Baladandayuthapani V, et al. Mucin20 Modulates Proteasome Capacity through c-Met Signaling and Predicts Proteasome Inhibitor Sensitivity in Myeloma. Leukemia. (under revision)

6.Shirazi F, Jones RJ, Singh RK, Kuiatse I, Berkova Z, et al. Activating KRAS, NRAS, and BRAF Mutants Enhance Proteasome Capacity and Reduce Endoplasmic Reticulum Stress in Multiple Myeloma. Proc Natl Acad Sci U S A. (under revision)

References available upon request.

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