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An NCI-designated Comprehensive Cancer Center, affiliated with the University of Pittsburgh School of Medicine
Research
Finding the right member is just a click away.
Our laboratory studies the formation and repair of DNA damage in nuclear and mitochondrial genomes. We are particularly interested in the structure and function of proteins that mediate DNA repair and the role of oxidative stress in human disease. We use state-of-the-art single molecule, biochemical and cell biology tools.
Dr. van Londen is an ABIM-certified medical oncologist and geriatrician whose research interests focus on a wide variety of topics relevant to cancer survivorship via multiple collaborations. However, her primary research focus relates to the assessment and management of adverse effects of adjuvant endocrine therapy in older cancer survivors.
Our research focuses on various aspects of T cell regulation and function:
(1) Mechanistic Focus:
(a) Immune Regulation: Regulatory T cells (Tregs): Identification of novel Treg molecules and their function; mechanism of Treg function; regulation of Treg stability via Nrp1 and other pathways; IL-35 signaling and mechanism of action; novel Ebi3 binding partner; IL-10 & IFNy function; neuron-immune interactions.
(b) Immune Regulation: Inhibitory Molecules: Identification of novel inhibitory receptors (IR) and their mechanisms; immune modulation of T cell subsets by LAG3; PD1 and NRP1; PD1-LAG3 synergy; mechanism of CD8+ and CD4_ T cell exhaustion; protein engineering to develop novel therapeutics.
(c) Structure-function analysis of T cell receptor (TCR):CD3 complex and LAG3 signaling: Mechanism of TCR:CD3 signaling; modulation & control of TCR signaling by IRs.
(d) Systems Immunology: Single cell systems approaches (transcriptomic & epigenomic) to hypothesis test, hypthesis generate and discover; technology and algorithm development; multispectral imaging.
(2) Disease Focus:
(a) Cancer: Biology of LAG3/PD1, IL-35 and NRP1 in mouse models of cancer and also in samples from treatment-naive patients or immunotherapy recipients; primary focus on solid tumors – head & neck, melanoma, lung, ovarian, breast cancer, with some work on pancreatic, GI and glioma cancers, and pediatric solid malignancies; novel approaches for therapeutic translation; biomarker discovery.
(b) Autoimmune and Inflammatory Disease: Impact, function & insufficiency of Tregs and IRs in several autoimmune and inflammatory disease with emphasis on models of autoimmune diabetes (NOD), EAE and asthma; development of therapeutic approaches (enhance Treg stability; IR agonists.
Dr. Villanueva's research focuses on the development of medical diagnostic and therapeutic strategies based on ultrasound and ultrasound contrast agents (gas-filled microspheres, or microbubbles). Her work has consistently bridged fundamental imaging sciences with translational biomedical research. As an Established Investigator of the American Heart Association, she has been a leader in the development of microbubbles for the assessment of myocardial perfusion, and ultrasound molecular imaging with targeted microbubbles for the detection of inflammatory and angiogenic endothelial markers in pre-clinical models of heart disease. Dr. Villanueva's lab has pioneered the development and application of microbubbles as molecular probes, and acoustic detection strategies for optimizing imaging sensitivity. Her lab group has applied fundamental principles of ultrasound and the physics of microbubble acoustic behaviors to develop novel targeted molecular therapeutics, whereby nucleic acid loaded microbubbles (siRNA, miRNA, plasmid), in the presence of precisely tuned ultrasound, selectively enhance membrane permeability and deliver payloads to the target site. These studies are conducted at the Center for Ultrasound Molecular Imaging and Therapeutics, a translational multidisciplinary research facility which epitomizes the reciprocal relationship between imaging sciences and biomedical translational research.
Dr. Liza C. Villaruz is an Associate Professor of Medicine at the University of Pittsburgh and UPMC Hillman Cancer Center and Co-Leader of the Immunotherapy and Drug Development Center at Hillman. She is a clinical and translational investigator in lung cancer with a focus on early drug development. She has active involvement in current clinical trials and a strong track record of successful development of institutional clinical trials with the National Cancer Institute and with industry partners.
My major research interests center around the discovery of small molecules with phenotypic assays in clinically relevant cellular and whole organism models. It is becoming increasingly clear that better models of the in vivo milieu are needed to improve the discovery of new drug candidates. Zebrafish, C. elegans, and Drosophila in particular provide unique opportunities to discover novel potential therapeutics using functional assays in a living animal as a complement to cellular and tissue model approaches. Together with members in the Departments of Neurology and Developmental Biology, I have established methodology for zebrafish chemical screening, generated automated image analysis tools for quantification of reporter gene expression, and automated neurobehavioral assays in multiwell plate formats. Currently, active zebrafish discovery projects include kidney and heart regeneration, angiogenesis and vascular malformations, early safety assessment, and neurodegenerative diseases. Cancer-related research efforts include the discovery of small molecule modulators of mitogen-activated protein kinase phosphatases (MKPs), PUMA, profilin-1, and estrogen receptor alpha as treatments for metastatic breast and colon cancer.
