Anda M. Vlad, MD, PhD
Associate Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, Department of Immunology, University of Pittsburgh, School of Medicine Director, MWRI Flow Cytometry Core Director, MWRI Summer Undergraduate Research Program
The Vlad Lab explores mechanisms of disease pathogenesis and immune surveillance in ovarian cancer and precursor lesions, and tests novel preventive and therapeutic approaches using a combination of highly versatile preclinical models and clinical specimens.
Our investigations have focused on immuno-oncology using either vaccines (MUC1), immune biologics (Interleukin-2) or immune checkpoint blockade (anti-PD-L1). Results from our phase II trial of intraperitoneal IL-2 in patients with platinum-resistant or platinum-refractory ovarian cancer show positive correlation between IFNγ- secreting CD8 T cells at early time points and survival. Our work provides important evidence for IP IL-2 in platinum-resistant ovarian cancer and identifies several immune correlates of survival.
Via collaborations with clinicians at Magee-Womens Hospital of UPMC, the lab is working on identifying mechanisms of early ovarian carcinogenesis from cancer precursor lesions. We recently implemented a biomarker discovery approach focusing on micro-RNA (miRNAs) and inflammation/immunity. Our findings demonstrate that tissue and blood gene signatures are not overlapping but rather complementary and that distinct plasma miRNA expression patterns may serve as highly specific and sensitive diagnostic biomarkers to discriminate between healthy, endometriosis, and EAOC cases.
Results from our inflammation profiling studies revealed that one third of the patients with endometriosis carry a tumor-like inflammation profile, suggesting that cancer-like immune signatures may develop earlier, in patients classified as clinically benign. Gene expression analyses revealed the complement pathway as most prominently involved in both endometriosis and EAOC and point to previously unknown roles of complement in endometriosis and EAOC.
Ongoing projects focus on epithelial to mesenchymal transition (EMT) and new therapies, including chemo-immune therapy for metastatic ovarian cancer.
- Zhang L Ma T, Brozick J, Babalola K, Budiu R, Tseng G and Vlad AM, 2Effects of Kras
activation and Pten deletion alone or in combination on MUC1 biology and epithelial to mesenchymal transition in ovarian cancer. Oncogene, January 2016. In Press.
- Graw S Meier R, Minn K, Bloomer C, Godwin AK, Fridley, Vlad AM, Beyerlein P and Chien J. Robust gene expression and mutation analyses of RNA-sequencing of formalin-fixed diagnostic tumor samples. Scientific Reports. 2015;5:12335
- Mony JT, Zhang L, Ma T, Grabosch S Tirodkar T, Brozick J, Tseng G, Elishaev E, Edwards
RP, Huang H and Vlad AM. Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor immune responses in a human MUC1- expressing preclinical ovarian cancer model. Cancer Immunology Immunotherapy 2015;64(9):1095-108.
- Ocak M, Gillman A, Bresee J, Zhang L, Vlad AM, Müller C, Schibli R Edwards B, Carolyn J.
Anderson CJ and Gach MJ. Folate receptor-targeted multimodality imaging of ovarian cancer in a novel syngeneic mouse model. Molecular Pharmaceutics 2015;12(2):542-53.
- Suryawanshi S, Huang X, Elishaev E, Budiu RA, Zhang L, Kim S, Donnellan N, Mantia-
Smaldone G, Ma T, Tseng G, Lee T, Mansuria S, Edwards RE and Vlad AM. Complement Pathway is Frequently Altered in Endometriosis and Endometriosis-Associated Ovarian Cancer. Clinical Cancer Research Oct 2014,
- Tirodkar TS, Budiu RA, Elishaev E, Zhang L, Mony JT, Brozick J, Edwards RP and. Vlad AM. MUC1 positive, Kras and Pten driven mouse gynecologic tumors replicate human tumors and vary in survival and nuclear grade based on anatomical location. PLoS One 2014;9(7):e102409.
- Parikh RA, Appleman LJ Bauman JE, Sankunny M, Lewis DW, Vlad AM, Gollin SM.
Upregulation of the ATR-CHEK1 pathway in oral squamous cell carcinomas. Genes Chromosomes Cancer. 2014; 53(1):25-37.
- Suryawanshi S*, Vlad AM*, Lin HM, Mantia-Smaldone G, Laskey R, Lee M, Lin Y,
Donnellan N, Klein-Patel M, Lee T, Mansuria S, Elishaev E, Budiu R, Edwards RP, Huang X. (*Authors with equal contributions). Plasma microRNAs as novel biomarkers for endometriosis and endometriosis-associated ovarian cancer. Clinical Cancer Research 2013;19(5):1213-24. Manuscript recommended to F1000Prime by Faculty of F1000 “as being of special significance in its field”.
- Budiu RA, Elishaev E, Brozick J, Lee M, Edwards RP, Kalinski P and Vlad AM.
Immunobiology of human mucin 1 in a preclinical ovarian tumor model. Oncogene. 2013;32(32):3664-75.
- Zhang L, Vlad AM, Milcarek C and Finn OJ. Human mucin MUC1 RNA undergoes different types of alternative splicing resulting in multiple isoforms. Cancer Immunol Immunother. 2013;62(3):423-35.
- Flint MS, Budiu RA, Teng PN, Sun M, Stolz DB, Lang M, Hood BL, Vlad AM, and Conrads T. Restraint stress and stress hormones significantly impact T lymphocyte migration and function through specific alterations of the actin cytoskeleton. Brain Behav Immun. 2011;25(6):1187-96.
- Budiu RA, Mantia-Smaldone G, Elishaev E, Chu T, Thaller J, McCabe K, Lenzner D,
Edwards RP and Vlad AM. Soluble MUC1 and serum MUC1-specific antibodies are potential prognostic biomarkers for platinum-resistant ovarian cancer. Cancer Immunol Immunother. 2011;60(7):975-84.
- Budiu R, Diaconu I, Chrissluis R, Dricu A, Edwards RP, Finn OJ, & Vlad AM. Mice
progressing to human mucin 1 (MUC1)-positive ovarian endometriosis-like lesions develop anti-MUC1 antibodies and show increased Foxp3 positive T cells in regional lymph nodes. Dis Model Mech, 2009;2(11-12):593-603.
- Vlad AM, Budiu RA, Lenzner DE, Wang Y, Thaller JA, Colonello K, Crowley-Nowick PA,
Kelley JL, Price FV, Edwards RP. A phase II trial of intraperitoneal interleukin-2 in patients with platinum-resistant or platinum-refractory ovarian cancer. Cancer Immunol Immunother. 2010;59(2):293-301.
- Ryan SO, Vlad A, Jean Gariépy, & Finn OJ. Tumor-associated glycopeptides of the tumor antigen MUC1 are not subject to self-tolerance and improves immune responsiveness in the MUC1 transgenic mouse. Biol Chem,390(7):611-8, Jul. 2009.
- Vlad A, Kettel J, Alajez N, Carlos C, & Finn OJ. Review article. MUC1 Immunobiology:
From discovery to clinical applications. Adv Immunol, 2003;82:249-93.
- Vlad A, Muller S, Cudic M, Paulsen H, Otvos L, Georg-Hanisch F, & Finn O. Complex
Glycans remain intact during the processing of MUC1 glycopeptides by dendritic cells and affect T cell recognition of MHC class II-restricted peptides. J Exp Med, 196(11): 1435-46, 2002.
For additional publications, see: (Pubmed or other online collection) http://www.ncbi.nlm.nih.gov/myncbi/collections/bibliography/43141884/