Victor Tseng

Research was conducted in the laboratory of Dr. David Guidot in the Emory University Alcohol and Lung Biology Center. In critically ill patients, chronic alcohol abuse has been identified as a potent risk factor for the development of acute respiratory distress syndrome (ARDS), often manifesting with heightened severity. Alcohol impairs redox homeostasis within the alveolus, resulting in decreased phagocyte function and increased epithelial permeability. The hallmark of the abnormal response to… Show more

Research was conducted in the laboratory of Dr. David Guidot in the Emory University Alcohol and Lung Biology Center. In critically ill patients, chronic alcohol abuse has been identified as a potent risk factor for the development of acute respiratory distress syndrome (ARDS), often manifesting with heightened severity. Alcohol impairs redox homeostasis within the alveolus, resulting in decreased phagocyte function and increased epithelial permeability. The hallmark of the abnormal response to alcohol-induced oxidative stress is inappropriate downregulation of the Nrf2-regulated antioxidant response element (Nrf2-ARE). Using a murine model of chronic alcohol exposure, I performed experiments in vitro on primary pulmonary fibroblasts to elucidate the mechanism by which this occurs. With significant guidance and navigation from junior faculty, I showed that chronic ethanol ingestion results in TGFβ-1 activation, and this directly mediates Nrf2-ARE repression2. I also identified distinct transciptional profiles in the lungs of mice subjected to transient versus chronic alcohol, dominated by biphasic expression of activating transcription factor-3 (ATF3), likely potentiating TGFβ1 signaling acutely. I gained proficiency in workhorse techniques such as RT-qPCR, antisense RNA manipulation, cell culture, and basic protein analysis. Show less

This research was performed, during medical school, under the guidance of Dr. David Yang, an associate professor of Pathology at the University of Wisconsin-Madison. I devoted most of my elective rotation time to the Hematopathology service and flow cytometry core. I performed a study of the outcomes of patients with de novo absolute peripheral blood lymphocytosis (count ≥ 5 × 106 cells/mL) detected incidentally on routine lab draws. This work was impelled by a need to develop evidence-based… Show more

This research was performed, during medical school, under the guidance of Dr. David Yang, an associate professor of Pathology at the University of Wisconsin-Madison. I devoted most of my elective rotation time to the Hematopathology service and flow cytometry core. I performed a study of the outcomes of patients with de novo absolute peripheral blood lymphocytosis (count ≥ 5 × 106 cells/mL) detected incidentally on routine lab draws. This work was impelled by a need to develop evidence-based screening pathways to efficiently distinguish reactive from clonal neoplastic lymphocytosis, and optimize the use of reflex manual pathologist smear review and flow cytometric testing. In a retrospective review of 1170 cases flagged by the automated hematology analyzer over two years, I collated data on clinical outcomes, flow cytometry results, and diagnostic codes. We determined that manual review could be foregone in 49.7% of cases without sacrificing test performance, if patient age and cell count could be used as independent discriminators. The project contributed to consensus criteria for manual pathologic review and proper utilization of flow cytometry. Incremental changes in the laboratory workflow were implemented, based on these conclusions. This work imparted experience with data acquisition, automated hemocytometry, and quality improvement. Show less

Following my undergraduate training, I gained employment in the R&D industry sector, at InBios International Inc, a medical diagnostics firm specializing in the fabrication of immunoassays for the rapid detection of highly transmissible zoonotic diseases. My primary assignment was the development of protocols and methods for high volume testing of hybridoma-derived antibodies or recombinant antigens against blood samples derived from patients with a range of vector-borne infections. After… Show more

Following my undergraduate training, I gained employment in the R&D industry sector, at InBios International Inc, a medical diagnostics firm specializing in the fabrication of immunoassays for the rapid detection of highly transmissible zoonotic diseases. My primary assignment was the development of protocols and methods for high volume testing of hybridoma-derived antibodies or recombinant antigens against blood samples derived from patients with a range of vector-borne infections. After significant effort in validation and calibration, I was successful in establishing a high-throughput protein microarray platform for screening large libraries of patient sera. The process was harnessed in a DoD-sponsored initiative to deliver a rapid assay for Dengue Virus (DENV) infection. A significant and exciting challenge was the differentiation of DENV serotypes, given the crucial need to identify patients at risk of Dengue Hemorrhagic Fever (DHF), a very fulminant form of disease mediated by antibody-dependent enhancement (ADE) during metachronous infection with differing viral strains. My work garnered a patent, and contributed to FDA 501(k) approval of two sandwich ELISA packages for diagnosis of Dengue Virus infection via detection of IgM or non-structural protein-1 (NS1) respectively. The IgM kit is now in wide use at several reference laboratories and field hospitals domestically and abroad. In the course of this project, I gained invaluable experience with protein microarrays, recombinant DNA technology, lateral flow immunoassays, ELISA development, and processing of clinical samples. Show less

I joined the laboratory of Dr. Gerry Smith at Fred Hutchinson Cancer Research Center (FHCRC), in the role of a work study student. I wrote my undergraduate capstone thesis here. In the fission yeast, Schizosaccharomyces pombe, I studied how homologous recombination was suppressed at centromeres. With their high tandem repeat content, centromeres would ordinarily be hotspots for recombination. Inappropriate centromeric crossover between sister chromatids during miosis is believed to drive… Show more

I joined the laboratory of Dr. Gerry Smith at Fred Hutchinson Cancer Research Center (FHCRC), in the role of a work study student. I wrote my undergraduate capstone thesis here. In the fission yeast, Schizosaccharomyces pombe, I studied how homologous recombination was suppressed at centromeres. With their high tandem repeat content, centromeres would ordinarily be hotspots for recombination. Inappropriate centromeric crossover between sister chromatids during miosis is believed to drive chromosome missegregation and translocations, leading to aneuploidy and congenital defects. Using pericentromeric flanking markers encoding trophic genes, I carried out a classical genetic analysis. Fission of S. pombe can be used to model the production of daughter products of meiosis, and the inheritance of haplotypes of these flanking alleles was used to measure linkage equilibrium (frequency of recombination). We found that the RNA-induced silencing complex (RISC) uses outer repeat-derived siRNAs to home into the centromere, and that Clr4 [histone H3 lysine N-methyltransferase] piggybacks on this complex to direct hypermethylation, thereby repressing recombination. My specific contribution to the project was the generation of 9 yeast strains, including a Dicer-1 knockout, and analysis of over 650 recombination events by genotyping of spores. I graduated from university at the midpoint of this project, and was pleased to see that these strains were instrumental in the full genetic analysis. I was competitively awarded a Mary Gates Endowment for Research [Bill and Melinda Gates Foundation], which further supported my tuition and expenses. My thesis, entitled “RNA Interference and Genetic Stability at Centromeres” achieved highest honors within the department. This early lab experience was formative, and kindled my interest in the basic sciences. I acquired proficiency with insertional mutagenesis, techniques of vector design, subcloning, and DNA transformation. Show less

Development of systems, algorithms, and controls, for automatic ventilator-driven titration of PEEP and tidal volumes such than local solutions are found for simultaneous maximization of lung compliance (CRS) and minimization of alveolar dead space (VD).

Projects focused on defining the role of hyaluronan polysaccharides in the maintenance of pulmonary vascular health and disease. Using mouse hypoxia models in genetically modified backgrounds (e.g. knockout of extracellular superoxide dismutase), I am able to study the effect of oxidative stress on matrix integrity in great detail.