Vincent C. Luca

Vincent C. Luca
Moffitt Cancer Center · Department of Drug Discovery

Doctor of Philosophy

About

48
Publications
5,409
Reads
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1,803
Citations
Citations since 2016
40 Research Items
1655 Citations
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Introduction
Vincent C. Luca currently works at the Department of Drug Discovery, Moffitt Cancer Center. Vincent does research in Biochemistry, Immunology and Structural Biology. His current project is 'Molecular Mechanisms of Notch Signaling.'
Additional affiliations
August 2012 - present
Stanford University
Position
  • PostDoc Position
Description
  • Cancer Research Institute Irvington Postdoctoral Fellow
March 2006 - May 2012
Washington University in St. Louis
Position
  • PhD Student
Education
August 2005 - December 2011
Washington University in St. Louis
Field of study
  • Molecular Biophysics
August 2001 - May 2005
Johns Hopkins University
Field of study
  • Biophysics

Publications

Publications (48)
Article
Notch receptor activation initiates cell fate decisions, and is distinctive in its reliance on mechanical force and protein glycosylation. The 2.5 angstrom crystal structure of the extracellular interacting regions of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms...
Article
Full-text available
Notch receptors guide mammalian cell fate decisions by engaging the proteins Jagged and Delta-like (DLL). The 2.3 angstrom resolution crystal structure of the interacting regions of the Notch1-DLL4 complex reveals a two-site, antiparallel binding orientation assisted by Notch1 O-linked glycosylation. Notch1 epidermal growth factor-like repeats 11 a...
Conference Paper
Background Lymphocyte activation gene 3 (LAG3) was recently validated as a target for next-generation immune checkpoint inhibitors. However, unlike PD-1 and CTLA-4, we have a poor molecular-level understanding of the LAG3 immunosuppression mechanism. We determined the structure of the LAG3 ectodomain to gain insight into its architecture and assemb...
Conference Paper
Background We designed a novel bispecific T-cell engager (BiTE) targeting the somatostatin receptor (SSTR), which is overexpressed by well-differentiated neuroendocrine tumors (NETs). In our BiTE, the single chain variable fragment (scFV) based anti-SSTR domain is replaced by 2 molecules of somatostatin-14 (SST14), the hormone that physiologically...
Article
Full-text available
The Notch pathway converts receptor-ligand interactions at the cell surface into a transcriptional response in the receiver cell. In recent years, synthetic Notch systems (synNotch) that respond to different inputs and transduce different transcriptional responses have been engineered. One class of synNotch systems uses antibody-antigen interaction...
Article
Full-text available
The Notch pathway regulates cell fate decisions and is an emerging target for regenerative and cancer therapies. Recombinant Notch ligands are attractive candidates for modulating Notch signaling; however, their intrinsically low receptor-binding affinity restricts their utility in biomedical applications. To overcome this limitation, we evolved va...
Preprint
Full-text available
Despite reports of striking outcomes, immunotherapy efficacy in melanoma is limited to subsets of patients 1, 2 . Combining immunotherapies with other modalities has yielded limited improvements but also adverse events requiring cessation of treatment ¹ . In addition to ineffective patient stratification, efficacy can be impaired by paucity of tumo...
Article
Full-text available
The immune checkpoint receptor lymphocyte activation gene 3 protein (LAG3) inhibits T cell function upon binding to major histocompatibility complex class II (MHC class II) or fibrinogen-like protein 1 (FGL1). Despite the emergence of LAG3 as a target for next-generation immunotherapies, we have little information describing the molecular structure...
Preprint
Full-text available
The Notch pathway converts receptor-ligand interactions at the cell surface into a transcriptional response in the receiver cell. In recent years, synthetic Notch systems (SynNotch) that respond to different inputs and transduce different transcriptional responses have been engineered. One class of synNotch systems uses antibody-antigen interaction...
Preprint
The Notch pathway regulates cell fate decisions and is an emerging target for regenerative and cancer therapies. Recombinant Notch ligands are attractive candidates for modulating Notch signaling; however, their intrinsically low receptor-binding affinity restricts their utility in biomedical applications. To overcome this limitation, we evolved va...
Article
Full-text available
Alterations in genes encoding for proteins that control fucosylation are known to play causative roles in several developmental disorders, such as Dowling-Degos disease 2 and congenital disorder of glycosylation type IIc (CDGIIc). Recent studies have provided evidence that changes in fucosylation can contribute to the development and progression of...
Article
Blockade of the inhibitory receptor TIM-3 shows efficacy in cancer immunotherapy clinical trials. TIM-3 inhibits production of the chemokine CXCL9 by XCR1⁺ classical dendritic cells (cDC1), thereby limiting antitumor immunity in mammary carcinomas. We found that increased CXCL9 expression by splenic cDC1s upon TIM-3 blockade required type I interfe...
Article
Full-text available
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate investigation of pathologies including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. We generated long-term feeder-free, chemically defined...
Article
Full-text available
The G protein-coupled bile acid receptor (GPBAR) conveys the cross-membrane signaling of a vast variety of bile acids and is a signaling hub in the liver–bile-acid–microbiota–metabolism axis1–3. Here, we report the cryo-EM structures of GPBAR–Gs complexes stabilized by either the high-affinity P3954 or the semisynthesized bile acid derivative INT-7...
Article
Gamma delta (γδ) T cells infiltrate most human tumors, but current immunotherapies fail to exploit their in situ major histocompatibility complex-independent tumoricidal potential. Activation of γδ T cells can be elicited by butyrophilin and butyrophilin-like molecules that are structurally similar to the immunosuppressive B7 family members, yet ho...
Preprint
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human dis...
Preprint
Full-text available
G protein-coupled bile acid receptor (GPBAR) is a membrane receptor that senses bile acids to regulate diverse functions through Gs activation. Here, we report the cryo-EM structures of GPBAR-Gs complexes stabilized by either high-affinity P395 or the semisynthesized bile acid derivative INT-777 at 3-Aring resolution. These structures revealed a la...
Article
Full-text available
Secreted R-spondin1-4 proteins (RSPO1-4) orchestrate stem cell renewal and tissue homeostasis by potentiating Wnt/β-catenin signaling. RSPOs induce the turnover of negative Wnt regulators RNF43 and ZNRF3 through a process that requires RSPO interactions with Leucine-rich repeat-containing G-protein coupled receptors (LGRs), or through an LGR-indepe...
Article
Full-text available
The growing availability of complex structures in the Protein Data Bank has provided key insight into the molecular architecture of protein–protein interfaces. The remarkable diversity observed in protein binding modes is paralleled by a tremendous variation in binding affinities, with interaction half-lives ranging from days to milliseconds. Withi...
Preprint
Full-text available
Secreted R-spondin1-4 proteins (RSPO1-4) orchestrate stem cell renewal and tissue homeostasis by potentiating canonical Wnt/Beta-catenin signaling. RSPOs induce the turnover of negative Wnt regulators RNF43 and ZNRF3 through a process that requires RSPO interactions with either Leucine-rich repeat containing G-protein coupled receptors (LGRs) or he...
Article
The Notch signalling pathway mediates cell fate decisions and is tumour suppressive or oncogenic depending on the context. During lung development, Notch pathway activation inhibits the differentiation of precursor cells to a neuroendocrine fate. In small-cell lung cancer, an aggressive neuroendocrine lung cancer, loss-of-function mutations in NOTC...
Article
Full-text available
The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling compo...
Article
Importance: Characterizing variant viruses can reveal new information about the lifecycle of Hepatitis C virus (HCV) and the roles played by different viral genes. However, it is difficult to recapitulate high levels of diversity in the laboratory because of limitations in the HCV culture system. To overcome this limitation, we engineered a librar...
Article
s: CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY The goal of our study is to establish the structural basis for Notch receptor-ligand interactions, a critical signaling event for mammalian cell fate determination and the pathogenesis of many cancer...
Article
Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates immune cell homeostasis and has been used to treat a range of disorders including cancer and autoimmune disease. IL-2 signals via interleukin-2 receptor-β (IL-2Rβ):IL-2Rγ heterodimers on cells expressing high (regulatory T cells, Treg) or low (effector cells) amounts of IL-2Rα (CD25). Wh...
Article
Full-text available
St. Louis encephalitis virus (SLEV) is a mosquito borne flavivirus responsible for several human encephalitis outbreaks over the last 80 years. Mature flavivirus virions are coated with dimeric envelope (E) proteins that mediate attachment and fusion with host cells. E is a class II fusion protein, the hallmark of which is a distinct dimer-to-trime...
Article
Full-text available
Japanese encephalitis virus (JEV) is the leading global cause of viral encephalitis. The JEV envelope protein (E) facilitates cellular attachment and membrane fusion and is the primary target of neutralizing antibodies. We have determined the 2.1-Å resolution crystal structure of the JEV E ectodomain refolded from bacterial inclusion bodies. The E...
Article
A recent study with flaviviruses suggested that structural dynamics of the virion impact antibody neutralization via exposure of ostensibly cryptic epitopes. To determine whether this holds true for the distantly related hepatitis C virus (HCV), whose neutralizing epitopes may be obscured by a glycan shield, apolipoprotein interactions, and the hyp...
Article
Full-text available
The E2 glycoprotein of hepatitis C virus (HCV) mediates viral attachment and entry into target hepatocytes and elicits neutralizing antibodies in infected patients. To characterize the structural and functional basis of HCV neutralization, we generated a novel panel of 78 monoclonal antibodies (MAbs) against E2 proteins from genotype 1a and 2a HCV...
Article
Flaviviridae are a family of enveloped, positive-stranded RNA viruses responsible for a variety of diseases including encephalitis, hemorrhagic fever and hepatocellular carcinoma. The envelope (E) proteins that coat the outer surface of these viruses provide the molecular machinery that drives receptor interaction and membrane fusion. The assignmen...

Questions

Question (1)
Question
We regularly express proteins recombinantly using the baculovirus system, but the cost of linearized baculovirus DNA has been steadily increasing. We are presently using vectors derived from pVL1393, so the bacmid would have to be compatible with those vectors. We are therefore hoping to purify our own DNA for co-transfection with our transfer vectors.

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Projects

Projects (3)
Project
Unraving the complexity of the immune response in human diseases, including chronic inflammatory intestinal disease and COVID-19.