Srdan M. Dragovic,

Ph.D.

Dept. of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, 300 Cedar Street TAC S410 New Haven, CT, 06520 ac5pu6@r.postjobfree.com

Education

2012-present Yale University School of Medicine (New Haven, CT) Associate Research Scientist in Section of Infectious Diseases, Dept. of Internal Medicine

Project: Plasmodium infection begins when anopheline mosquitoes inject sporozoites, with saliva, into a vertebrate host. Antiserum raised against Anopheles gambiae salivary glands protected mice from mosquito-borne Plasmodium infection, and an antigen recognized by this antiserum, A. gambiae TRIO (AgTRIO), participated in immunity. The Plasmodium liver burden and parasitemia of mice administered AgTRIO antiserum, and exposed to Plasmodium berghei-infected mosquitoes, was significantly lower than in control animals. Active immunization with AgTRIO also protected against mosquito-borne P. berghei infection. A combination of AgTRIO antiserum and antibodies against Plasmodium circumsporozoite protein - a promising vaccine candidate in human trials – further decreased P. berghei infection in mice. Two-photon microscopy demonstrated that AgTRIO antiserum reduced sporozoite movement in the murine dermis. AgTRIO can serve as arthropod- based target against Plasmodium independently, or with a pathogen- specific immunogen, to combat malaria. This work has been accepted for publication (Dragovic et al, Cell Host Microbe, April 2018).

Advisor: Dr. Erol Fikrig

2005-2011 Vanderbilt University School of Medicine (Nashville, TN) Ph.D. in the Department of Microbiology and

Immunology

Dissertation: Proteasomes, TAP, and Endoplasmic Reticulum-Associated Aminopeptidase Associated with Antigen Processing (ERAAP) Control CD4+ TH Cell Responses by Regulating Indirect Presentation of MHC Class II- Restricted Cytoplasmic Antigens (Dragovic et al, Journal of Immunology, 2011)

Advisor: Dr. Sebastian Joyce; Thesis Committee chair: Dr. Luc Van Kaer 2003-2005 University of Belgrade, Faculty of Pharmacy (Belgrade, Serbia) Graduate studies- introductory courses in the Department of Medical Biochemistry.

Advisor: Dr. Svetlana Ignjatovic

1996-2003 University of Belgrade, Faculty of Pharmacy (Belgrade, Serbia) B. Sc. in the Pharmacy and Medical Biochemistry Dissertation: Anticoagulant and anti-inflammatory role of protein C Advisor: Dr. Svetlana Ignjatovic and Dr. Nada Majkic-Singh Graduated with High Distinction as the top student of the Class 2002/2003 Research and Work Experience

2012-present Yale University School of Medicine

Dept. of Internal Medicine, Section of Infectious Diseases, New Haven, CT

My work is directed towards understanding how malaria parasite uses an Anopheles gambiae salivary gland protein, AgTRIO, to enhance transmission to mice. The Plasmodium liver burden and parasitemia of mice administered AgTRIO antiserum, and exposed to Plasmodium berghei-infected mosquitoes, was significantly lower than in control animals. Active immunization with AgTRIO also protected against mosquito-borne P. berghei infection. Moreover, in humanized mice, AgTRIO antiserum provided protection against a human pathogen, Plasmodium falciparum, transmitted by mosquitoes. Two-photon microscopy demonstrated that AgTRIO antiserum reduced sporozoite movement in the murine dermis. AgTRIO can serve as arthropod-based target against Plasmodium independently, or with a pathogen-specific immunogen, to combat malaria.

Techniques: I have used a combination of qRT-PCR, molecular cloning, sgRNA-CRISPR, flow cytometry, co-immunoprecipitation, siRNA, dsRNA, retroviral gene transduction, protein production and purification (E.coli, S2

Drosophila and Express five expression system) and mass spectrometry, as well as other large-scale screening methods, including yeast surface display assay, to survey for protein-protein interactions. 2005-2011: Vanderbilt University School of Medicine Dept. of Microbiology and Immunology, Nashville, TN Under the guidance of Dr. Sebastian Joyce, published first author research paper with no additional revisions asked by reviewers The body of the work dealt with the role that proteasomes, TAP and

ERAAP, but not tapasin, play in negatively affecting presentation of allogeneic, microbial, tumor and self-MHC class II-restricted antigens which greatly affect resulting CD4+ TH cell responses; and Heat shock protein 90 and calreticulin serve as chaperones for the indirectly presented MHC class II-restricted antigens

Techniques: Utilized flow cytometry; ELISpot; mass spectrometry and proteomic data analysis; retroviral gene transduction, RNA, DNA and gene knock-down; also protein manipulation using molecular biology techniques including co- immunoprecipitation; reverse phase-HPLC; work with experimental animals (mice); worked with bacterial and viral pathogens (Listeria monocytogenes and vaccinia virus) etc.

2003-2005: Clinic and Hospital Center “Dr. Dragisa Misovic”, Belgrade, Serbia Worked in Central Biochemical and Hematology laboratory. Utilized various spectrophotometric kinetic, or end-point protein/enzyme, and lipid techniques; thin layer chromatography; cancer markers; electrolytes, etc.

2003-2005: University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia Worked with Dr. Svetlana Ignjatovic. Focus was foundational course work in anticipation of thesis project in Medical Biochemistry. 1996-2003: University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia Completed course work for degree in pharmacy (pharmacology) and medical biochemistry

Experimental work was conducted in the area of medical biochemistry, enzymology, clinical chemistry, microbiology and immunology, toxicology, pharmaceutical chemistry at the Clinical Center of Serbia, the Emergency Center of Serbia, Belgrade and the Faculty of Pharmacy laboratories.

Also, physical, analytical, inorganic and organic chemistry methods etc. Publications:

1. Dragovic S.M., Agunbiade TA, Freudzon M, Yang J, Hastings AK, Schleicher T, Zhou X, Craft S, Chuang YM, Gonzalez F, Li Y, Hrebikova G, Tripathi A, Mlambo G, Almeras L, Ploss A, Dimopoulos G, and Fikrig E, (2018). Immunization with AgTRIO, a protein in Anopheles saliva, contributes to protection against Plasmodium infection in mice. (Manuscript accepted in Cell Host Microbe).

2. Conway MJ, Watson AM, Colpitts TM, Dragovic S.M., Li Z, Wang P, Feitosa F, Shepherd DT, Ryman KD, Klimstra WB, Anderson JF, Fikrig E. (2014). Mosquito saliva serine protease enhances dissemination of dengue virus into the mammalian host. J.

Virol., 88: 164-175.

3. Wang J, Zhang Y, Zhao YO, Li MW, Zhang L, Dragovic S, Abraham NM, Fikrig E. (2013). Anopheles gambiae circumsporozoite protein-binding protein facilitates plasmodium infection of mosquito salivary glands. J. Infect. Dis., 208: 1161-1169.

4. Spencer CT, Dragovic S.M., Conant SB, Gray JJ, Zheng M, Samir P, Niu X, Moutaftsi M, Van Kaer L, Sette A, Link AJ, Joyce S. (2013). Sculpting MHC class II-restricted self and non-self peptidome by the class I Ag-processing machinery and its impact on Th- cell responses. Eur. J. Immunol., 43: 1162- 1172.

5. Dragovic S.M., Hill T., Christianson G.J., Kim S., Elliott T., Scott D., Roopenian DC, L. Van Kaer L. and Joyce S. (2011). Proteasomes, TAP, and Endoplasmic Reticulum-associated aminopeptidase associated with antigen processing control CD4+ TH cell responses by regulating indirect presentation of MHC class II- restricted cytoplasmic antigens. J. Immunol., 186: 6683-6692.

6. Lee K., Gudapati P., Dragovic S., Spencer C., Joyce S., Killeen N., Magnuson MA., Boothby M. (2010). Mammalian target of rapamycin protein complex 2 regulates differentiation of TH1 and TH2 cell subsets via distinct signaling pathways. Immunity, 32: 743-753. 7. Bezbradica JS., Gordy LE., Stanic AK., Dragovic S., Hill T., Hawiger J., Unutmaz D., Van Kaer L., Joyce S. (2006). Granulocyte-macrophage colony-stimulating factor regulates effector differentiation of invariant natural killer T cells during thymic ontogeny. Immunity, 26: 487-497. 8. Yan J, Parekh VV, Mendez-Fernandez Y, Olivares-Villagómez D, Dragovic S,. Hill T, Roopenian DC, Joyce S, Van Kaer L. (2006). In vivo role of ER associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. J. Exp. Med., 203: 647-659. 9. Spencer CT, Gilchuk P., Dragovic SM., Joyce S. (2010). Minor histocompatibility antigens: presentation principles, recognition logic and the potential for a healing hand. Curr. Opin. Organ Transplant., 15: 512-525. Honors and Membership:

1996 Member, Society of Medical Biochemistry, Belgrade, Serbia 2001 Award as an outstanding student, Royal Norwegian Embassy in Belgrade, Serbia

2003 Award as the best student in Pharmacy and Medical Biochemistry class 2002/2003, Faculty of Pharmacy, University of Belgrade 2004 Award, “Prof. Dr. Ivan Berkes” for an outstanding student in pharmacy and medical biochemistry, Society of Medical Biochemistry, Belgrade, Serbia 2004 Volunteer practice in Central Biochemical Laboratory of Clinical and Hospital Center

“Dr. Dragisa Misovic”, Belgrade, Serbia

2014 Member, American Heart Association

Awards, honors and presentations:

• Immunization with AgTRIO, a protein in Anopheles saliva, contributes to protection against Plasmodium infection in mice,, Infectious Diseases and Rheumatology Seminar Series, Yale University School of Medicine, 2018

• Investigation of Anopheles salivary gland proteins that modulate Plasmodium transmission, Infectious Diseases and Rheumatology Seminar Series, Yale University School of Medicine, 2014

• Identification of interactions between Anopheles gambiae salivary gland and Plasmodium surface proteins, Infectious Diseases and Rheumatology Seminar Series, Yale University School of Medicine, 2013

• Destructive roles of TAP and ERAAP on indirect presentation of MHC class II- restricted cytoplasmic antigens, Microbiology and Immunology Department Research in Progress Seminar Series, Vanderbilt University School of Medicine, 2008

• The role of innate- sterile immunity during minor histocompatibility antigen response, poster presentation, Microbiology and Immunology Department retreat, Fall Creek Falls, 2008,

• MHC class I antigen processing machinery regulates MHC class II associated antigenic peptide repertoire, Microbiology and Immunology Department Research in Progress Seminar Series, Vanderbilt University School of Medicine, 2007

• Society of Medical Biochemists of Serbia, Prof. Dr. Ivan Berkes award for the best student in pharmacy and medical biochemistry, Faculty of Pharmacy, University of Belgrade, Class 2002/2003

• ‘Royal Norwegian Embassy award for the outstanding undergraduate student, Serbia,

2001.

Teaching experience

1. Teaching Assistant, Vanderbilt University Interdisciplinary Graduate Program Bioregulation Course Defense Mechanisms (IGP 302) in 2007, 2010 and 2011. 2. Teaching Assistant, Laboratory, Vanderbilt University School of Medicine

Microbiology and Immunology Course (VMS 1) for the first year Medical students, 2008

3. Xia Zhou, visiting scientist from Soochow University Medical School, Jiangsu, China 4. Sam Craft, laboratory assistant,

5. Alfred Jiang, Yale undergraduate student.

Conferences attended

Annual Immune Epitope Database and Discovery Workshop Meeting, held in La

Jolla, CA, 2008

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