Flow Cytometry Molecular Biology

Tatyana N. Milovanova, M.D., Ph.D.

The Center for Breakthrough Medicines

*** ********* **., **** ** Prussia, Philadelphia, PA, 19406;

w.t. 215-***-****, h.t 215-***-**** E-mail: ad5qhk@r.postjobfree.com

Technical Expertise

Current and comprehensive expertise across flow cytometry, molecular biology, cell biology, biochemistry, molecular enzymology techniques, with strong background in gene engineering, signal transduction.

•Extensive knowledge of and experience in immune and autoimmune disease, drug discovery research, epigenetic factors in the projects investigating the role of dendritic cells and human Tregs normally and in pathophysiological mechanisms of diseases, lung transplantation and tumorigenesis; cell proliferation, angiogenesis, tumor suppression and autoimmunity, mesenchymal stem cells biology ischemia-reperfusion injury in lung transplantation, decompression sickness mechanisms, lung physiology and diseases, oxidative stress, cell proliferation assays, immunology, allergology, and ecology etc.

•Animal models of diseases, numerous clinical trials

•Expertise in multicolor flow cytometry (4-18 colors), surface and intracellular staining, stem cells (mesenchymal and adipose-derived) isolation, culture, detection, microparticles isolation; neutrophils, FOXP3 Tregs, lymphocytes, dendritic cells, endothelial cells, subtypes detection, and quantification, T-cell polarization and cytokines production by dendritic cells, flow cytometric proliferation assays (CFSE, PKH26 etc), apoptosis detecting (TUNEL, annexin V/PI etc), cytokines, cell cycle; excellent knowledge of CellQuest, ModFit, ModList, FlowJo, BD Biosciences DiVa software; ViaCell etc. programs; blood and lavage proliferation assays, 3H-thymidine incorporation assay,

•Clinical database analysis and presentations using Microsoft Excel, StatView, Sigma Stat, Microsoft Word, Power Point; Affimetrix Microarray (GeneSpring, Ingenuity, EASE, DAVID, FireSpot etc. programs), PRISM software

•Signaling pathways

•Confocal and Multi-photon microscopy

•In situ hybridization technique

•Microbiome

•Experience with ELISA and immunoassays

•World expertise in endothelial cell culture under shear stress in the cartridges, microparticles and stem cells proliferation in vivo and in vitro

•Over 20 years of experience in clinical laboratories, including hormones chromatography, Northern blot, Western blot, Affimetrix microarray, cDNA, RNA isolation, qPCR, confocal microscopy and MetaMorph Images, expertise in computer programs (PowerPoint, Image Tools, Adobe PhotoShop, PaintPro, SigmaStat, SigmaPlot, EndNote etc.).

MOLECULAR BIOLOGY

Recombinant DNA analysis methods: isolation of plasmid and page DNA, recombinant DNA techniques (DNA subcloning and plasmid construction); PCR; oligonucleotide directed in vitro mutagenesis, site directed and deletion mutagenesis. Computer analysis of DNA and protein sequences; luciferase reporter assays. DNA/Protein analysis software: DNASIS-MAC 2.0, Oligo 2.0; NIH image; Clone Manager7 Un-Scan It gel 4.3

CELL BIOLOGY

Long-term experience with culture of various mammalian cell lines such as fibroblasts, epithelial cells, endothelial cells, T-cells, melanoma cell lines, keratinocytes as well as manipulation of these cell lines in cell-based assays. Experience in transient transfection of DNA and siRNA (calcium phosphate method, lipofection, Amaxa electroporation system); stable transfection of mammalian cells; cell cloning; luciferase reporter assay; immunofluorescent staining; confocal microscopy. Basic cell biology and cell cycle techniques: cell fractionation, sucrose gradient isolation of centrosomes, lysosomes and melanosomes, centrosome spin-down assay, microtubules nucleation assay. Cell sorting on magnetic beads.

PROTEIN BIOCHEMISTRY & IMMUNOCHEMISTRY

Chromatography: thin layer, gel filtration, ion-exchange, immunoaffinity. Electrophoresis: analytical and preparative - SDS, native. Immunochemical analysis: ELISA, Western blot, immunoprecipitation, protein immunoprecipitation on magnetic beads. In vitro kinase assay. Subcellular fractionation. Protein-protein interactions. Duolink® in situ proximity assay.

CHEMICAL ENZYMOLOGY

Basic enzymology techniques, working with system of hydrated reversed micelles, various techniques for covalent and non-covalent modification of proteins. Circular Dichroizm.

PROFESSIONAL SOFTWARE (WINDOWS / MAC)

DNA / Protein Analysis Software: DNASIS-MAC 2.0, Oligo 2.0; NIH image (ImageJ); Clone Manager7. Protein Structure Analysis Software: 3D Molecular viewer (spdbv). Internet database searches and database analysis. Additional: CANVAS, ClustalW, Un-Scan It Gel 4.3, MetaMorph, Microsoft Office, Outlook, Adobe Illustrator, Adobe Photoshop, Corel Draw, Criket Graph, SigmaPlot, SigmaStat

EDUCATION

Senior Scientist, Flow Cytometry, Department of Flow Cytometry, the Center of Breakthrough Medicines

Senior Research Investigator, Department of Periodontics, Dental School, University of Pennsylvania, USA

Scientist IV, Children’s Hospital of Philadelphia, University of Pennsylvania, USA

Senior Research Investigator, Hyperbaric Oxygenation Therapy Laboratory, Institute for Environmental Medicine, University of Pennsylvania, USA

Research Associate, Hyperbaric Oxygenation Therapy Laboratory, Institute for Environmental Medicine, University of Pennsylvania, USA

Adjunct Assistant Professor at University of Philadelphia (Anatomy and Physiology courses for professionals and medical students).

Research Associate, Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, USA

Postdoctoral Fellowship, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, USA

Continued Medical Education (Medical Genetics), Academy of Advanced Education, St. Petersburg, Russia

Fellowship in Pulmonology, II Moscow Medical University, Moscow, Russia

Residency in Family and Emergency Medicine, Saratov Medical University, Saratov, Russia

PhD in Pulmonology, Bronchitis and Pneumonia with Obstructive Syndrome in the Early Childhood (Pathogenesis and Ecological Aspects) Moscow Medical University II, Moscow, Russia

MD in Pediatrics (Honors), Saratov Medical University, Saratov, Russia

Over 200 publications and lectures

Extensive university level teaching experience (teaching Pediatrics, Anatomy and Physiology class for medical students (Russia and USA)

EMPLOYMENT HISTORY AND HIGHLIGHTS

2022-recent Senior Scientist, Flow Cytometry, the Center for Breakthrough Medicines

2021-2022 Senior Scientist, Flow Cytometry, HUP, University of Pennsylvania

2017-2021 Senior Research Investigator, University of Pennsylvania

Mentor: Dr. Dana Graves, Dean of Research, Professor of Periodontology

Projects:

1. The role of dendritic cells in periodontal disease

2. Wound healing and Diabetes

3. Femur Fracture and bone repair

2015-2016 Research Scientist IV, Children’s Hospital of Philadelphia

Mentor: Dr. Wayne Hancock, Professor of Transplantation Immunology

Projects: T-cell immunologic response in transplantation, schizophrenia, FOXP3+ regulatory T-cells (Tregs), the role of human Treg function in healthy donors, after organ transplantation and in tumorigenesis, role of HDACs in Tregs function, ischemia-reperfusion injury in lung transplantation, projects involving cell proliferation, angiogenesis, tumor suppression and autoimmunity mostly related to autoimmune diseases and rare/orphan diseases, transplant immunology, angiogenesis, neovasculogenesis, mesenchymal stem cells biology

2008-2014 Sr. Research Investigator, HBO2 laboratory, IFEM, University of Pennsylvania

Mentor: Dr. Thom S.R., Professor of Emergency Medicine

Projects: Mechanisms of Decompression Sickness,

Stem Cells proliferation and differentiation in vivo;

Microparticles in normal and pathophysiological conditions

Artificial Blood Vessels MP in neurological patients (aneurisms)

TBI

Neutrophil activation in heart failure

Decompression sickness pathogenesis, determining the mechanisms of decompression sickness, creating of model of angiogenesis in vivo.

2006-2008 Research Associate, HBO2 laboratory, IFEM, University of Pennsylvania Mentor: Dr. Thom S.R., Professor of Emergency Medicine

Projects: Mechanisms of Decompression Sickness,

Stem Cells proliferation and differentiation in vivo

Investigation and determining the mechanisms of decompression sickness, creating of model of angiogenesis in vivo.

2006-2008 Adjunct Professor at University of Philadelphia

(Anatomy and Physiology class, teaching medical students)

2002-2006 Research Associate, IFEM, University of Pennsylvania

Mentor: Dr. Fisher A.B., Prof. of Physiology and Medicine,

Projects: Shear Stress, ROS and Endothelial Cell Proliferation

Investigated the role of Reactive Oxygen Species generation in the Endothelial cells, Proliferation using Flow cytometry method, confocal microscopy, Western &Northern blots, Microarray assay etc.

2000-2002 Postdoctoral Research Fellow,

Mentor: Dr. Rossman, M.D., Prof. of Medicine,

Dr. University of Pennsylvania, Pulmonary, Allergy and Critical Care Division

Project: A flow cytometric test for beryllium sensitivity

Conducted immunological and clinical research of patients with chronic beryllium disease by using 4-color flow cytometry method and lymphocytes proliferation test.

1996-2000 Medical Business Consultant, IVC of Philadelphia

Mentor: Dr. Nancy Gilboy, Director, Nobel Prize Nominee

International Visitors Council, Philadelphia, PA

Provided business consulting and interpreting services for short-term programs in medical education and business for the government visitors from the countries of the former Soviet Union. Assisted in directing short-term education programs for foreign medical doctors provided by Hahnemann and Allegheny Universities

1992-1996 Clinical & Research Assistant Professor, Department of Pediatrics, Saratov Medical University, Saratov, Russia

Taught courses in Pulmonary, Clinical Genetics, Nephrology, and conducted research on problems of lungs and kidneys associated with environmental pollution and allergy; and consulted patients with similar diseases

EDITORIAL BOARD: 1. Open Journal of Respiratory Diseases (OJRD)

2. Journal of Biomarkers

LANGUAGES: English and Russian, both fluent; French, reading knowledge

HONORS

•2013 GLIIFCA-22 2013, Best Poster Award, September 27-29, 2013, Detroit, MI, USA

•2013 46th UHMS Annual Scientific Meeting, June 13-15, 2013, Orlando, Florida, Presidential Award for the Best Oral Presentation and Poster

•2012 45th UHMS Annual Scientific Meeting, June 21-23, 2012, Phoenix, AZ, Presidential Award for the Best Oral Presentation and Poster

•2011 44th UHMS Annual Scientific Meeting, June 21-23, 2011, Phoenix, AZ,

Presidential Award for the Best Oral Presentation and Poster

•2010 GLIIFCA-19 2010, Best Poster Award, October 8, 2010, Detroit, MI, USA

•2009 Penn Flow 2009 Best Poster Award, June 24, 2009, University of Pennsylvania

•2008 Hyperbaric Research Prize from an international scientific panel of the Baromedical Research Foundation, for “basic science contributions that have provided a vital foundation for the practice of hyperbaric medicine

•2008 Albert R. Behnke Award from the Undersea and Hyperbaric Medical Society, for “outstanding scientific contributions to advances in the undersea or hyperbaric medical field - bone marrow stem cell HBO2 effects"

•2007 Paul Bert Award from the Undersea and Hyperbaric Medical Society, for” excellence in the practice of hyperbaric medicine and basic research”

•2007 Best Poster Award 7th Annual Undersea & Hyperbaric Medical Society Scientific Meeting, June 14-16, 2007, Hawaii, Maui

•Eleventh Annual Great Lakes International Imaging and Flow Cytometry Association, Plenary Speaker Award, October 6, 2002, Detroit, MI, USA

•GLIIFCA Caltag Laboratories Award for the Outstanding Poster, October 10, 2001, Philadelphia, PA, USA

•Pediatrician with Highest Qualification in Pulmonary and Family Medicine, 1994, Russia

•Special Scholarship (Lenin’s Award-an extremely prestigious award given to a very limited number of extraordinary medical students by the government), 19781979, Russia

MEMBERSIP

•International Society for Stem Cell Research (ISSCR), since 2012

•IRM, University of Pennsylvania, since 2008

•American Society of Physiology, since 2003

•American Thoracic Society, since 2001

•Great Lake International Imaging and Flow Cytometry Society, since 2000

•National Pediatric Society of Russia, 1979-present

CERTIFICATES

•Supervisory Skills Certificate program June 12, 2013

•Business Writing May 2013

•Project Management February, 2013

KEY MANUSCRIPTS

1.Ding Z. Qui M, Alharbi MA, Huang T, Pei X, Tatyana Milovanova, Jiao H, Liu M, Dana T. Graves FOXO1 expression in chondrocytes modulates cartilage production and removal in fracture healing. Bone, 2021 Jul;148:115905. doi: 10.1016/j.bone.2021.115905. Epub 2021 Mar 1. PMID: 33662610

2.Liang Song, Yingming Yang, Tatyana Milovanova, Dongxu Qiu, Lijia Guo, Adriana Cabrera-Ortega, Jia Ni, Chao Song, Yongwon Cho, Carlos Rossa Jr, Dana T. Graves FOXO1 regulates dendritic cell induced T-helper phenotypes and pathologic consequences (JCI, in review)

3.Dana T Graves, Tatyana N Milovanova. Mucosal Immunity, the FOXO1 Transcription Factor and Periodontal Diseases, Frontiers in Immunology, section Mucosal Immunity (Review).Front Immunol. 2019 Nov 29;10:2530. doi: 10.3389/fimmu.2019.02530. eCollection 2019.PMID: 31849924

4.Alharbi MA, Zhang C, Lu C, Milovanova TN, Yi L, Ryu JD, Jiao H, Dong G, O'Connor JP, Graves DT. FOXO1 Deletion Reverses the Effect of Diabetic-Induced Impaired Fracture Healing. Diabetes. 2018 Dec;67(12):2682-2694. doi: 10.2337/db18-0340. Epub 2018 Oct 2.

5. Jeon HH, Yu Q, Lu Y, Spencer E, Lu C, Milovanova T, Yang Y, Zhang C, Stepanchenko O, Vafa RP, Coelho PG, Graves DT FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds. J Pathol. 2018 Jul;245(3):258-264. doi: 10.1002/path.5075. Epub 2018 Apr 20

6.Leif-Erik Bohman, John Riley, Tatyana N. Milovanova, Matthew R. Sanborn, Stephen R. Thom, and William M. Armstead. Microparticles Cause Disordered Cerebrovascular Autoregulation After Pediatric Traumatic Brain Injury (NEU-20153885). J Neurotrauma. 2016 Jan 15;33(2):168-74.

7.Madden D., Thom SR, Milovanova TN.,Yang M., Bhopale VM, Ljubkovic M, Dujic Z. Exercise before SCUBA Diving Ameliorates Decompression-Induced Neutrophil Activation. Med Sci Exerc 2014 Feb 26; 2014 Oct;46(10):1928-35

8.Fukaya E, Margolis DJ, Miller CJ, Milovanova TN, Papadopoulos M, Thom SR. Endothelial progenitor cell mobilization following acute wound injury. Wound Repair Regen. 2013 Nov; 21(6):907-8.

9.Marvin Heyboer I, Tatyana N. Milovanova, Susan Wojcik, William Grant, Mary Chin, Kevin R. Hardy, David Lambert, Christopher Logue, Stephen R. Thom Stem cell mobilization by hyperbaric oxygen – changes with oxygen dosage. Stem Cell Research 2014 May; 12(3):638-45. doi: 10.1016/j.scr.2014.02.005. Epub 2014 Feb 28

10.Pietrofesa BS, Jason B Turowski, Evguenia Arguiri BS, Tatyana N Milovanova, Charalambos C Solomides, Stephen R Thom and Melpo Christofidou-Solomidou.

Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration. J Pulm Respir Med 2013, 3: 158163

11.Xu J, Yang M, Kosterin P, Salzberg BM, Milovanova TN, Bhopale VM, Thom SR.Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction. Toxicol Appl Pharmacol. 2013 Dec 1; 273(2):410-7.

12.Yang M, Kosterin P, Salzberg BM, Milovanova TN, Bhopale VM, Thom SR. Microparticles generated by decompression stress cause central nervous system injury manifested as neurohypophisial terminal action potential broadening. J Appl Physiol (1985). 2013 Nov; 115(10):1481-6.

13.Thom SR, Milovanova TN, Bogush M, Yang M, Bhopale VM, Pollock NW, Ljubkovic M, Denoble PJ, Madden D, Lozo M, Dujic Z. Bubbles, microparticles and neutrophil activation: changes with exercise level and breathing gas during openwater SCUBA diving. J Appl Physiol. 2013 May; 114(10):1396-405.

14.Thom SR, Bhopale VM, Milovanova TN, Yang M, Bogush M, Buerk DG Nitric-oxide synthase-2 Linkage to Focal Adhesion Kinase in Neutrophils Influences Enzyme Activity and β2 Integrin Function. J Biol Chem. 2013 Feb 15;288(7):4810-8

15.Thom SR, Yang M, Bhopale VM, Milovanova TN, Bogush M, Buerk DG. Intramicroparticle nitrogen dioxide is a bubble nucleation site leading to decompression - induced neutrophil activation and vascular injury. J Appl Physiol. 2012.

16.Thom SR, Bhopale VM, Milovanova TN, Yang M, Bogush M. Thioredoxin reductase linked to cytoskeleton by focal adhesion kinase reverses actin Snitrosylation and restores neutrophil β2 integrin function. J Biol Chem. 2012 Aug 31;287(36):30346-57

17.Sanborn M, Thom SR, Bohman LE, Stein SC, Levine J; Milovanova TN, Maloney Wilensky E, Frangos S; Kumar M. Temporal Dynamics of Microparticle Elevation Following Subarachnoid Hemorrhage J. of Neurosurgery, 2012 Sep;117(3):579-86

18.Thom SR, Milovanova TN, Bogush M, Bhopale VM, Yang M, Bushmann K, Pollock NW, Ljubkovic M, Denoble PJ, Dujic Z. Microparticle production, neutrophil activation and intravascular bubbles following open-water SCUBA diving. J Appl Physiol. 2012 Apr; 112 (8):1268-78.

19.Yang M, Milovanova TN, Bogush M, Uzun G, Bhopale VM, Thom SR. Microparticles enlargement and altered surface proteins after air decompression

are associated with inflammatory vascular injuries. J Appl Physiol. 2012 Jan; 112(1):204-11.

20.Thom SR, Bhopale VM, Yang M, Bogush M, Huang S, Milovanova TN. Neutrophil beta-2 integrin inhibition by enhanced interactions of vasodilator-stimulated phosphoprotein with S-nitrosylated actin. J Biol Chem. 2011 Sep 16; 286(37):32854-65.

21.Thom SR, Milovanova TN, Yang M, Bhopale VM, Sorokina EM, Uzun G, Malay DS, Troiano MA, Hardy KR, Lambert DS, Logue CJ, Margolis DJ. Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. Wound Repair Regen. 2011 Mar-Apr; 19 (2):149-61.

22.Thom SR, Yang M, Bhopale VM, Huang S, Milovanova TN. Microparticles initiate decompression-induced neutrophil activation and subsequent vascular injuries. J. Appl Physiol. 2011 Feb;110 (2):340-51.

23.Thom SR, Bhopale VM, T.N. Milovanova, Hardy KR, Logue CJ, Lambert DS, Troxel AB, Ballard K, Eisinger D. Plasma biomarkers in carbon monoxide poisoning. Clin Toxicol (Phila). 2010 Jan; 48(1):47-56.

24.E.M.Sorokina, S.I. Feinstein, T.N. Milovanova, A.B.Fisher. Identification of the amino acid sequence that targets peroxiredoxin 6 to lysosomal-like structures of lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2009 Nov; 297(5):L87180.

25.T. N. Milovanova, Veena M. Bhopale, Elena M. Sorokina, Jonni S. Moore Thomas K. Hunt, Martin Hauer-Jensen, Omaida C. Velazquez and Stephen R. Thom. Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo. J. Appl Physiol. 2009 Feb;106(2):711-28

26.Tatyana N. Milovanova, Jonni S. Moore, Elena M. Sorokina, Thomas K. Hunt, Omaida C. Velazquez and Stephen R. Thom. Lactate stimulates vasculogenic stem cells via the thioredoxin system and engages an autocrine activation loop involving hypoxia-inducible factor 1 Mol Cell Biol. 2008 Oct;28(20):6248-61

27.Stephen R. Thom, Veena M. Bhopale, David J. Manchini, Tatyana N. Milovanova. Actin S-Nitosylation inhibits Neutrophil β2-Integrin Function JBC, 2008 Apr 18;283(16):10822-34

28.T. Milovanova, Madesh M., Hawkins B., Chatterjee S., Sorokina E., DeBolt K., Moore J., and Fisher AB. Caveolae are an essential componenet of the pathway for endothelial cell signaling associated with abrupt reduction of shear stress Biochim Biophys Acta. 2008 Oct;1783(10):1866-75

29.Michael J. Gallagher, Jr. Nachiket Vaze, Shailesh Gangoli, Victor N. Vasilets, Alexander F. Gutsol, Tatyana N. Milovanova, Shivanti Anaudan, Donna M. Murasko and Alexander A. Fridman. Rapid inactivation of airborne bacteria using atmospheric pressure dielectric barrier grating discharge, IEEE Transactions on Plasma Science, Vol.35, NO. 5, October, 2007, pp.1501-1510

30.T. Milovanova. Comparative analysis between CFSE flow cytometric and tritiated thymidine incorporation tests for beryllium sensitivity, Clinical Cytometry, 2007 Jul;72B(4):265-275

31.T.Milovanova, S. Chatterjee, Y. Manevich, I. Kotelnikova, K. DeBolt, M. Muniswamy, J.S. Moore, A.B. Fisher. Lung Endothelial cell proliferation with decreased shear stress is mediated by reactive oxygen species, AJP-Cell Physiology, 2006 Jan;290(1):C66-76

32.M. Muniswamy, B. Hawkins, T. Milovanova, P. Satish, Ramachandra Rao, K.

Sharma, T. Kurosaki, Fisher A.B. Selective role for superoxide in IP3 receptormadiated mitochondrial dysfunction and endothelial apoptosis. J Cell Biol, 2005, Sep 26;170(7):1079-90

33.ST. Scanlon, T. Milovanova, Y. Tomer, S.J. Russo, MF. Beers, A. Haczku. Surfactant Protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses, Respiratory Research, Respir Research, 2005, Aug 24, 6:97

34.T. Milovanova, S. Popma, S. Cherian, J.S. Moore, M.D. Rossman. Flow cytometric test for beryllium sensitivity, Clinical Cytometry, 2004, 60B(1):23-30

35.T. Milovanova T, Manevich Y, Haddad A, Chatterjee S, Moore JS, Fisher AB: Endothelial cell proliferation associated with abrupt reduction in shear stress is dependent on reactive oxygen species. Antioxid Redox Signal 2004; 6(2): 245-58.

PATENTS

1.“Flow Cytometric Method and Kit for Metal-Induced Sensitivity”.

The US Patent Number is 60/558,500, filed 4/1/04. Docket number: P-7671-US Assignment Document of Patent from June 28, 2007. Final Approval 08/01/2011.

2.“Flow Cytometric Method of Detection for Endothelial Cell Proliferation in Confluent Cultures”, submitted 05/16/05, Docket #R3967 (pending).

3.“Flow Cytometric Test of Enumeration of Circulating Progenitor Cells in the Whole Human Blood”, submitted 06/11/07, Docket # U4871 (pending).

Grants and Contracts

Active Grants:

1.Microbioma grant till 2026

2.Epigenetics, dendritic cells R01 till 2025

3.Wound healing in diabetes R01 till 2026

1. 10/1/13 – 09/30/16 “Pharmacological inhibition of neutrophil adherence by nitric oxide”

Office of Naval Research N00014-12-10363 Annual Direct Cost: $ 240,646

Total Direct Cost: $626,272

This grant is to elucidate mechanisms for inhibition of murine neutrophil β2 integrin’s by nitric oxide.

Role: Co-Investigator

2. 07/01/13 - 06/30/16 “Microparticles, platelet-neutrophil aggregation and decompression sickness in a murine model”

Office of Naval Research N00014-13-10613 Annual Direct Cost: $ 208,913

Total Direct Cost: $1,253,755

The project examines perivascular oxidative stress and the role of microparticles in decompression stress.

Role: Co-Investigator

3. 07/01/13 - 06/30/16 “Microparticle production with decompression stress in human”

Office of Naval Research N00014-13-10614

Annual Direct Cost: $195,821

Total Direct Cost: $587,634

This project examines the microparticle production and neutrophil activation in humans performing experimental SCUBA dives and in injured divers who are suffering from decompression sickness.

Role: Co-Investigator

4. 09/01/12 – 08/31/17 “Stem cell mobilization in diabetes” National Institute of Diabetes and Digestive and Kidney Diseases

RO1 DK094260

Annual Direct Costs: $ 480,950

Total Direct Costs: $2,407,604

This project examines variations in circulating and wound margin stem cells in diabetics and their association with wound healing.

Role: Co-Investigator

5. 03/01/12 – 02/28/16 PI Gary Wu, M.D., Dr. Thom

“Microbiome responses to oxidative stress”

National Institute of General Medical Science

RO1 GM094260

Annual Direct Costs: $ 14,434 (sub-award)

Total Direct Costs: $ 57,736

This project will quantify gut oxygen levels of mice exposed to different partial pressures to provide a comprehensive evaluation of oxidative stress on the gut microbiome, its impact on bacterial community structure, and its relationship to the development of the “dysbiotic” microbiome associated with inflammatory bowel disease.

Role: Co-Investigator

Completed Grants:

6. 04/01/11 – 03/31/14 PI: David Margolis, M.D., Ph.D.

“Comparative Effectiveness of Adjunctive Devices for Prevention of Amputation in Diabetes”

Agency for Health Care Quality

Annual Direct Costs: $280,950

Total Direct Costs: $607,604

7. 03/01/12 – 06/30/13 “Pharmacological Inhibition of Neutrophil Adherence”

Office of Naval Research N00014-12-1-0420 Annual Direct Cost: $205,899

Total Direct Cost: $629,389

8. 04/15/06 – 05/01/12 “Hyperoxia and neutrophil adhesion”

Office of Naval Research N00014-06-01-0363

Annual Direct Cost: $ 248,595

Total Direct Cost: $ 1,260,000

9. 03/30/08 – 03/31/10 “Stem cell mobilization in diabetes”

National Institute of Diabetes and Digestive and Kidney Diseases

R21 DK080376

Annual Direct Cost: $ 136,875

Total Direct Cost: $ 275,000

10. 04/01/08 – 03/31/11 PI: Omaida Velazquez, M.D.

“Recruiting activated endothelial progenitor cells to wounds by hyperoxia and SDF-1a”

National Institute for General Medical Sciences R01 GM081570

Annual Direct Cost: $ 250,000

Total Direct Cost: $ 750,000

11. 04/01/08 – 10/01/09 “Biomarkers profiles for carbon monoxide poisoning”

National Institute for Environmental Health Science R43 ES016720

Annual Direct Cost: $ 68,000

Total Direct Cost: $ 98,000

12. 2014/09/22-2016/08/31 150049, Wyle Integrated Science and Engineering Group

Kochunov, Peter (PI)

QUASAR Acute MRI Changes in Association with Single Hypoxic Exposure

Annual Direct Cost: $ 250,000

Total Direct Cost: $ 750,000

To evaluate possible pathophysiology of altitude cerebral decompression sickness. This study involves exposing human volunteers to decompression to simulated altitude (hypobaric) conditions as done regularly by USAF personnel with and without concomitant hypoxia. Pre- vs. post- exposure studies include high resolution MRI, circulating cytokines and changes will be correlated with circulating microparticles, neutrophil and platelet activation.

Role: Co-Investigator

Interfacial mechanics in intravascular gas embolism.

13. 3/1/2008 - 2/28/2013

Principal Investigator: Dr. Thom SR; David M. Eckmann, PhD, MD

Agency: NIH Type: R01 HL060230 :

This project investigates how composition and nano-scale surface structure of biomaterials alters blood cell physiology.

Role: Co-investigator

PENDING:

Super resolution imaging and ultra-sensitive photonic analysis for cell and interfacial science.

Principal Investigator: Stephen R. Thom, MD, PhD

Agency: DOD Type: Defense University

Research Instrumentation Program

This grant is to develop a single-platform equipment array for imaging that incorporates a super-resolution microscope, Brewster angle microscope and a streaming Zeta potential analyzer. Role: Co-Investigator

DOCUMENTARY FILMS

•“The Right to be Protected”, Nigne-Volgskaya State Studio of Documental Films, Saratov, Russia, 1986

•“I Would Like to Tell More…”, Nigne-Volgskaya State Studio of Documental Films, Saratov, Russia, 1988

•“Endothelial Cells Culture in the FiberCell Cartridges” (John Caldwell), April, 2005

PRESENTATIONS

DENDRITIC CELLS

1.Milovanova TN, Y. Yang, L. Song, Y. Wang, D. Qiu, L. Guo and Graves DT T-cell polarization is controlled by activated FOXO1 in dendritic cells in regulation of susceptibility to periodontitis, abstract and poster, Research Day, May 16, 2019, University of Pennsylvania, Dental School

2.D. Graves. T. Milovanova, Y. Yang, L. Song, Y. Wang, D. Qiu, L. Guo FOXO1 Activation in Dendritic Cells Controls T-cell Polarization to Regulate Periodontal Disease Susceptibility, 2019 IADR/AADR/CADR General Session (Vancouver, BC, Canada)

MICROPARTICLES

•47th UHMS Annual Scientific Meeting, June 18-21, 2014, St. Lous, Missouri: Bubbles, Microparticles and Neutrophil Activation: Changes with Exercise Level and Breathing Gas during open-water Scuba Diving (oral presentation and poster, abstract A1)

•46th UHMS Annual Scientific Meeting, June 13-15, 2013, Orlando, Florida: Bubbles, Microparticles and Neutrophil Activation: Changes with Exercise Level and Breathing Gas during open-water Scuba Diving (oral presentation and poster, abstract A1)

•46th UHMS Annual Scientific Meeting, June 13-15, 2013, Orlando, Florida:Agerelated Changes in Bone Marrow Stem Cell Mobilization and Peripheral Recruitment are improved by Mesenchymal Stem Cells or Hyperbaric Oxygen (oral presentation and poster, abstract B21)

•45th UHMS Annual Scientific Meeting, June 21-23, 2012, Phoenix, AZ:Microp articles Production, Neutrophil Activation and Intravascular Bubbles following open-water Scuba Diving, 45th UHMS Annual Scientific Meeting, June 21-23, 2012, Phoenix (A4)

•45th UHMS Annual Scientific Meeting, June 21-23, 2012, Phoenix, AZ: Reversing

HBO2-mediated Neutrophil 2-Integrin Dysfunction: Role for Thioredoxin Reductase Linked to Focal Adhesion Kinase

•Tenth Annual PennFlow International Imaging and Flow Cytometry Association,

June 7, 2012, Philadelphia, PA, USA (poster), p. 8 Decompression-induced

Neutrophil Activation and Vascular Injuries Are Caused by Microparticles

•Twentieth Annual Great Lakes International Imaging and Flow Cytometry Association, October 8, 2011, Detroit, WI, USA (poster), p. 26 Decompression induced Neutrophil Activation and Vascular Injuries Are Caused by Microparticles

•WIP, University of Pennsylvania, Decompression-induced Neutrophil Activation and Vascular Injuries Are Caused by Microparticles, August 25, 2010

STEM CELLS MOBILIZATION AND DIFFERENTIATION

•13th ISSCR Annual Scientific Meeting, June 24-27,

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