The Nedelcu Lab's primary focus is cellular therapies and transfusion medicine. Our current project in clinical transfusion medicine is to elucidate the mechanism of allergic transfusion reactions.

The Nishimura Lab's research spans basic, translational and clinical research themes. Their clinical/translational projects focus on the use of biospecimens and correlation of morphometry with gene expression and genetic variation in disease-susceptibility. Basic research themes focus-on the regulation of cell-extracellular matrix interactions by integrins, the role of host-pathogen interactions in innate and adaptive immunity in the evolution of fibroinflammatory diseases, the activation and function of TGF-beta in epithelial-mesenchymal-immune cell interactions and in tumor immunobiology. Current projects include the role of TGF-beta and inflammation in fibroinflammatory diseases, genetic variation in regulation of TGF-beta activation in COPD, the role of paracrine TGF-beta activation by mesenchymal cells in the regulation of innate and adaptive immunity, the role of autophagy in lung injury and repair, the role of integrin structure in TGF-P activation and the role of TGF-beta in tumor immunity.

The Norris Lab's research interests focus on how the human immune system responds to viral infections and transfusion. Our early efforts centered on defining how HIV-specific CD4+ T cells contribute to control of viral infection. A second area of interest has been defining the earliest events of viral infections through study of subjects with HIV, West Nile virus, and hepatitis viruses. Some of our more recent projects include understanding how blood transfusion affects the immune system and modulates immune responses in transfusion recipients, including the role extracellular vesicles play in immune modulation.

The Ott Lab is interested in how viruses interact with the host cell. Through these interactions we hope to gain new insight into cellular processes and the viral life cycle. Currently, we focus on three pathogens-the human immunodeficiency virus (HIV-1), Zika virus, and the hepatitis C virus (HCV)-and three cellular processes-lipid droplets, transcriptional elongation, and immune reprogramming. We recently developed several human 3D organoid models in the lab and study how viruses spread in these models using single-cell RNA-Seq. Our research is relevant for efforts to eradicate HIV from patients, to alleviate fatty liver disease in chronic HCV infection, and suppress uncontrolled immune activation in virally infected patients or patients with autoimmunity.

The Pelka lab studies the cellular interactions that shape immune responses in human tumors, focusing on how these responses are regulated. Immune cells cannot execute their function in isolation, but require interactions with other immune and non-immune cells. We still only understand a very small number of these communication networks. Using a combination of large-scale genomic analyses and tissue imaging approaches, we have identified hubs in tumor tissues where tumor cells come into close contact with immune cells. By characterizing and perturbing the cells in these hubs, and the gene networks that are turned on in these cells, we aim to uncover novel ways to harness the immune system in the fight against cancer.

The Peng Lab is interested in how supportive niche cells modify the regenerative capacity of the stem cell, with the goal of deciphering cellular crosstalk that drives adaptive tissue regeneration. Our lab utilizes the lung as a model organ due to its immense cellular diversity and architectural complexity. Adult solid organs are composed of diverse cellular compartments with complex 3D organization that informs specific functions, with varying degrees of regenerative capacity in response to injury and tissue inflammation. While resident tissue stem cells play an important role in the regenerative process, they are located within a cellular ecosystem composed of various cell types that regulate stem cell function, including immune cells.

In the Perera Lab we study the mechanisms of autophagy-lysosome activation and how this organelle system contributes to cellular reprogramming in cancer. Autophagy and the lysosome function to capture and recycle diverse cellular and extracellular macromolecules. Our prior studies have identified transcription circuits essential for maintenance of autophagy and lysosome biogenesis in pancreatic cancer and our ongoing work focuses on identifying unique features and functions of these organelles in promoting tumor growth, immune evasion, metastasis and therapy resistance. We use a combination of techniques including organelle purification and biochemistry, immuno-fluorescence imaging, proteomics and metabolomics in cell lines, primary culture systems and genetically engineered mouse tumor models, to address how changes in organelle function in cancer cells and immune cells promote disease.

The Peterlin Lab uses molecular biology, immunology, virology and genetics to tackle intractable immunodeficiencies, be they the bare lymphocyte syndrome or AIDS. These approaches also find resonance in autoimmunity and cancer. In the process, these diseases and their pathogens educate us about human biology and evolution. Indeed, new paradigms in genomic stability, transcription, transport and intracellular traffic have been forthcoming from these studies. Our ultimate goals are to use this knowledge of basic molecular mechanisms to cure human diseases.

The Phillips Lab is broadly interested in how the molecular properties of viral proteins and antibodies constrain their evolution and co-evolution. Viral proteins and antibodies acquire amino acid substitutions at a rate orders of magnitude above most eukaryotic proteins. These substitutions can have pleiotropic consequences on protein stability, folding, and function. The lab is developing high-throughput evolution and phenotyping assays to determine how these properties, and trade-offs bettheyen them, constrain and potentiate the evolution of viral proteins and antibodies, and how this varies bettheyen distinct selection environments. These experimental platforms will enable them to (1) determine key constraints on protein evolution, (2) predict the emergence of new viral variants, and (3) design therapeutic strategies that are refractory to the development of resistance.

The Phillips laboratory is focused on understanding the dynamic interplay between brain tumor cells and their microenvironment. Specifically, we study how the immune response influences tumor progression and therapy resistance.

The Piao Lab investigates the molecular mechanisms underlying those diverse functions of microglia with a special focus on how they refine the brain circuit by regulating interneuron development and synaptic pruning. Microglia act as resident brain cells in regard to their involvement with neurogenesis, synapse refinement and modulation of neural circuits. At the same time, microglia express their macrophage ontogeny by virtue of responding to Damage Associated Molecular Patterns (DAMPs) generated by disease processes, aging and cell injury. The canonical macrophage-like responses of microglia may be reparative, injurious or maladaptive during neurodevelopment or neurodegeneration. Relatively little is known in molecular detail about these aspects of microglial physiology particularly in humans, yet the genetic architecture of neurodegenerative disease illustrates vividly that microglial responses can be crucial for the divergent trajectories of healthy development or aging versus disease.

The Pillai Lab employs a translational systems approach to investigate viral evolution, pathogenesis and persistence, with the goal of developing novel viral eradication strategies. We leverage the extensive biobank at Vitalant Research Institute (VRI) and invaluable collaborations with HIV/AIDS cohorts at UCSF to study the host-virus interface in vivo. We develop and implement unbiased approaches to identify key host immune factors that can be exploited as pharmacological targets and viral disease biomarkers. Our work thus far has elucidated the effects of anatomic compartmentalization on HIV evolution, the role of cell-intrinsic immunity in the antiviral potency of interferon, and the regulation of HIV transcription during suppressive antiretroviral therapy (ART).