A5017153880- Protein Structure and Dynamics
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Enzyme Structure and Function
- LGBTQ Health, Identity, and Policy
- Computational Drug Discovery Methods
- ATP Synthase and ATPases Research
- Advanced Proteomics Techniques and Applications
- Themes in Literature Analysis
- Gender Roles and Identity Studies
- Vibrio bacteria research studies
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Nanoplatforms for cancer theranostics
- Protein Kinase Regulation and GTPase Signaling
- Autophagy in Disease and Therapy
- Jewish Identity and Society
- Trace Elements in Health
- Cell death mechanisms and regulation
- Neuropeptides and Animal Physiology
- Pain Mechanisms and Treatments
Boston College
2024
University of Michigan
2024
Xilio Therapeutics (United States)
2022-2024
Northwestern University
2014-2024
University at Buffalo, State University of New York
2018
Johns Hopkins University
2012
Abstract Hereditary Parkinson’s disease is commonly caused by mutations in the protein kinase PINK1 or E3 ubiquitin ligase Parkin, which function together to eliminate damaged mitochondria. phosphorylates both Parkin and stimulate ubiquitination of dozens proteins on surface outer mitochondrial membrane. However, mechanisms recognizes specific for modification remain largely unexplored. Here, we show that C-terminal GTPase (cGTPase) primary substrate human Miro necessary sufficient efficient...
Trypanosoma brucei infection causes human African trypanosomiasis, also known as sleeping sickness, a disease with nearly 100% fatality rate when untreated. Current drugs are expensive, toxic, and highly impractical to administer, prompting the community explore various unique aspects of T. biology in search better treatments. In this study, we identified protein arginine methyltransferase (PRMT), Tb PRMT1, factor that modulates numerous biology. These include glycolysis life cycle...
Robust kinetochore-microtubule (kMT) attachment is critical for accurate chromosome segregation. G2/M-specific depletion of human Cdt1 that localizes to kinetochores in an Ndc80 complex-dependent manner leads abnormal kMT attachments and mitotic arrest. This indicates independent role addition its prototypic function DNA replication origin licensing. Here, we show directly binds microtubules (MTs). Endogenous or transiently expressed both spindle MTs kinetochores. Deletion mapping revealed...
A series of thiol-based glutamate carboxypeptidase II (GCPII) inhibitors have been synthesized with either a 3-(mercaptomethyl)benzoic acid or 2-(2-mercaptoethyl)benzoic scaffold. Potent were identified from each the two scaffolds IC(50) values in single-digit nanomolar range, including 2-(3-carboxybenzyloxy)-5-(mercaptomethyl)benzoic 27c and 3-(2-mercaptoethyl)biphenyl-2,3'-dicarboxylic 35c. Compound 35c was found to be metabolically stable selective over number targets related...
Abstract Offering insights from a research–practice partnership, we examine how five pre‐K–6 teachers discussed using LGBTQ+‐inclusive children's literature as backup to counter curricular censorship and community pushback.
ABSTRACT While it is currently estimated that 40 to 50% of eukaryotic proteins are phosphorylated, little known about the frequency and local effects phosphorylation near pharmaceutical inhibitor binding sites. In this study, we investigated how frequently may affect drug inhibitors target proteins. We examined 453 non‐redundant structures soluble mammalian bound available in Protein Data Bank (PDB). cross‐referenced these with data from PhosphoSitePlus database. Three hundred twenty‐two...
Abstract Cdt1 is a protein critical for DNA replication licensing and well-established to be binding partner of the minichromosome maintenance (MCM) complex. has also been demonstrated have an emerging, “moonlighting” role at kinetochore via direct microtubules Ndc80 However, it not known how structure conformations could allow these multiple, completely unique sets complexes. And while there exist multiple robust methods study entirely folded or unfolded proteins, structure-function studies...
Abstract PD-1/PD-L1 therapies have shown significant activity across a range of tumor types, however, 70-90% patients do not derive durable benefit. In preclinical settings, delivery PD-1 blockade and IL-2 agonism in cis via bispecific molecule, comprising antibody fused to IL-2, has demonstrated superior compared individual components or their combination. Targeting PD-1+ cells been drive unique differentiation path endowing CD8+ T with enhanced functionality. However, we show that the...
Abstract This article explores how undergraduate students enrolled in a postsecondary course centering LGBTQ+ young adult literature came to discursively construct notions of queer youth. Braiding postdevelopmental and poststructural theories childhood with theory, we interrogated what name as the (il)logics adolescence shaped who youth, construct, was could be for participants. Reading across classroom artifacts student talk about texts, our findings highlight shifting multiple offered by...
ABSTRACT Cdt1 is a mixed folded protein critical for DNA replication licensing and it also has “moonlighting” role at the kinetochore via direct binding to microtubules Ndc80 complex. However, unknown how structure conformations of could allow participate in these multiple, unique sets complexes. While robust methods exist study entirely or unfolded proteins, structure–function studies combined, folded/disordered proteins remain challenging. In this work, we employ orthogonal biophysical...
Amidst the backdrop of rising censorship legislation, it is important to understand influence teachers’ particular contexts on their perceptions potentially controversial texts and subsequent instructional choices. This study explores five in-service acts positioning observed in year-long antibias antiracist professional book club, which facilitated educators’ access such opened space for imagining ways incorporate them into classroom practice. The findings illuminate how teachers positioned...
Reading moments of classroom talk as text, we explored how prospective teachers in a Teaching Diverse Young Adult Literature course read and responded to Michael Muhammad Knight’s The Taqwacores , text with Muslim LGBTQIA+ theme. Thinking queer theory—and its constituent concept, homonationalism, more specifically—we examined discourses difference, both liberatory oppressive, were shaped notions collective acceptance, tolerance, inclusion intersected interpersonal contradictions...
Abstract Dysfunction in mitochondrial dynamics is believed to contribute a host of neurological disorders and has recently been implicated cancer metastasis. The outer membrane adapter protein Miro functions the regulation mobility degradation, however, structural basis for its roles remain unknown. Here, we report 1.7Å crystal structure N-terminal GTPase domain (nGTPase) human Miro1 bound unexpectedly GTP, thereby revealing non-catalytic configuration putative active site. We identify two...
The bacterial pathogen Vibrio cholerae use a type III secretion system to inject effector proteins into host cell. Recently, putative Toxic GTPase Activating Protein (ToxGAP) called outer protein E (VopE) was identified as T3SS substrate and virulence factor that affected mitochondrial dynamics immune response. However, biophysical structural characterization has been absent. Here, we describe solution NMR structure of the GTPase-activating (GAP) domain (73-204) VopE. Using size exclusion...
Abstract Although PD-1/PD-L1 therapies have shown significant activity across a range of tumor types, only subset patients (10-30%) achieve durable responses. With the goal improving response and application to therapies, we leveraged our proprietary Xilio Advanced Cytokine Therapies (X-ACT) platform develop PD1/IL2-ACT, PD-1 blocker enhanced with tumor-activated, engineered IL-2 agonist. The is blocked by protein domain that prevents IL-2Rβγ binding until activated in microenvironment...
Abstract Robust kinetochore-microtubule (kMT) attachment is critical for accurate chromosome segregation. G2/M-specific depletion of human Cdt1 that localizes to kinetochores in an Ndc80 complex-dependent manner, leads abnormal kMT attachments and mitotic arrest. This indicates independent role addition its prototypic function DNA replication origin licensing. Here, we show directly binds microtubules (MTs). Endogenous or transiently expressed both spindle MTs kinetochores. Deletion mapping...