Current Trainees

Adriana Sordida

Harnessing Protein Language Models to Identify Novel Sterol and Steroid-Binding Proteins: Advancing Physiology and Functional Insights

Steroids are essential lipids that play a critical role in maintaining cellular membrane integrity and regulating hormonal and metabolic processes, yet many of the proteins that bind to these molecules remain unidentified or uncharacterized. My research leverages recent advances in machine learning, particularly Protein Language Models (PLMs), to predict and identify novel proteins that interact with sterols and steroids. A significant focus is on discovering bile acid-interacting proteins in both humans and gut microbes, as bile acids, which are co-metabolites produced by the host and modified by gut microbiota, are involved in crucial signaling pathways. Recent findings suggest that these novel bile acids may interact with unidentified proteins, and by applying PLM-based methods, I aim to uncover proteins that mediate these interactions, offering new insights into host-microbiome communication. By integrating PLM and machine learning tools, this research seeks to discover novel proteins that could have significant implications for both human physiology and our understanding of sterol-related functions across different organisms.

Alexa Perez

Structural and biochemical investigation of ncRNA and RNA binding protein interactions

Focus on the structural interactions between novel non-coding RNAs and the formation of RNP with predicted RNA binding proteins. Structural information will be used to aid the biochemical evaluation of RNA and protein functionality. 

Anna Skrip

Uncovering the evolutionary history and medicinal potential of single-component flavin-dependent halogenases: an integrated approach 

We aim to harness the power of selectivity and green chemistry with flavin-dependent halogenases. We utilize bioinformatics and enzyme characterization to understand nature’s evolved mechanistic preferences and inform novel biosynthetic approaches in drug development.

Brian Pham

Structural and functional characterization of RNA polymerase pausing and riboswitch co-transcriptional folding

My research focuses on how RNA polymerase pausing influences the co-transcriptional folding and function of riboswitches, regulatory elements in mRNAs that directly bind ligands to modulate gene expression. Specifically, I aim to uncover the mechanisms that link riboswitch folding kinetics to their regulatory activity.

Caesar Tawfeeq

Conformational Dynamics of Wildtype and R201C Mutant G Stimulatory Protein Isoforms

As part of the Sunahara lab, my research involves applying computational biophysics tools and experimental techniques to characterize the conformational dynamics and molecular mechanisms of heterotrimeric G proteins. I am currently interested in understanding the differences between wildtype and R201C mutant of both the long and short splicing isoforms of G stimulatory proteins.

Christine Vu

Elucidating ERCC6L2-Mediated Liquid-Liquid Phase Separation and Protein Interactions in DNA Repair Pathways

This study investigates the role of ERCC6L2 in DNA repair, focusing on its potential involvement in liquid-liquid phase separation (LLPS) to form biological condensates. We aim to elucidate the dynamics of ERCC6L2 LLPS and its protein-protein interactions using live cell imaging and TurboID methodology. Findings will provide insights into the molecular mechanisms of DNA repair, highlighting ERCC6L2’s function in damage recognition and pathway selection, with implications for therapeutic targeting in DNA repair-related conditions.

Emerson Hall

Investigating high mannose binding lectins for applications as potential antiviral molecules

I aim to characterize the glycotypes of three unique lectins Oscillatoria agardhii agglutinin (OAA), Cyanovirin-N (CVN), and Griffithsin (GRFT) using biophysical techniques. Biolayer interferometry (BLI), nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC) will be utilized to provide kinetic, structural, and thermodynamic information respectively. I hope to dissect the factors underlying lectin specificity and mechanism behind multivalency.  

Jaqueline Lanzalotto

Mechanisms of RNA Localization in Aspergillus Nidulans

Protein synthesis is an essential component of cellular growth, survival and maintenance. Newly synthesized proteins can be transported by the intracellular trafficking machinery to where they are required in the cell. However, proteins can be locally translated rather than trafficked from their site of synthesis to their final destination. mRNA transport plays a pivotal role in enabling precise, on-site translation of transcripts. My research aims to understand the molecular mechanisms of mRNA localization in the filamentous fungus Aspergillus nidulans.

Kezia Jemison

Title: Probing Receptor Binding Domain Dynamics of the SARS-CoV-2 Spike Protein

I investigate the dynamics of the SARS-CoV-2 spike protein’s Receptor Binding Domain (RBD) within the Wuhan-2019/Wild-type (WT), Delta (Δ), and Omicron (Ο) strains via Hydroxyl Radical Protein Footprinting for comparison to Amaro Lab predictions aiming to explain the observed increased COVID-infectivity of emerging variants.

Kelly Isbell

Email: kisbell@ucsd.edu
Undergrad Institution: University of Virginia
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Itay Budin

Mechanisms of PTCH1-Mediated Membrane Remodeling in Hedgehog Signaling

The hedgehog (Hh) pathway receptor Patched (Ptch1) suppresses the G-protein coupled receptor Smoothened (Smo). Ligands that inhibit Ptch1, such as sonic hedgehog in vertebrates, control tissue patterning during embryogenesis and tissue repair post-embryogenesis. Insufficient Hh signaling leads to developmental defects, whereas overactivation leads to ectodermal cancers including basal cell carcinoma (BCC) and medulloblastoma. Loss-of-function Ptch1 mutations are responsible for 85% of BCCs, a cancer for which more than 1 million US patients are treated for each year. Despite the narrow equilibrium necessary for proper Hedgehog signaling, exactly how Ptch1 regulates Smo is unknown. Ptch1 has been proposed to transport cholesterol across or out of the plasma membrane (PM), which goes hand-in-hand with findings that Smo is itself activated by cholesterol. The ability of cholesterol to act as a second messenger is surprising due to its high abundance in the PM and ability to rapidly flip-flop between bilayer leaflets. Sequestering interactions between sphingomyelin (SM) and cholesterol have been proposed to limit the accessibility of cholesterol to protein binding partners, but have not been rigorously tested. Using FRET and NMR-based assays, I aim to biophysically characterize the effects of SM sequestration on cholesterol chemical activity and interleaflet flip-flop kinetics. Then, utilizing Ptch1 proteoliposomes, I will elucidate the means and direction through which Ptch1 remodels membrane cholesterol as well as the conformational dynamics that dictate Ptch1 activity and inhibition. Finally, orchestrating a powerful combination of confocal microscopy, solvatochromatic dyes, engineered protein biosensors, and pharmacological and genetic manipulations, I will investigate the fundamental interactions between Ptch1, Smo, SM, and cholesterol that dictate Hh signaling in biophysically complex, living cell membranes. My ultimate goal is to generate a seamless model that describes how Ptch1-mediated remodeling of membrane cholesterol accessibility or activity on other lipid species regulates Smo activation.

Benjamin Pollak

Alex Plonski

Email: aplonski@ucsd.edu
Undergrad Institution: University of Colorado, Denver
Current Program at UC San Diego: Biochemistry and Molecular Biophysics
Advisor: Galia Debelouchina

Structural and Mechanistic Investigations of Calcification in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a progressive eye disease that is most prevalent within aging populations and can lead to significant vision loss. AMD affects the macula on the central retina, where pathological extracellular deposits called drusen can be found between the sub-retinal pigment epithelium and Bruch’s membrane. These deposits consist of a core made up of extracellular lipids enriched with cholesterol, which are encased by calcium-phosphate debris known as hydroxyapatite with proteins associated on the surface. The protein substrates include the blood protein Vitronectin, and Alzheimer’s Disease associated proteins Amyloid beta and Tau. Despite the significance of drusen and their association with both AMD and neurodegenerative diseases, the understanding of their molecular-level structure, mechanisms of assembly, and the role of the associated proteins remains limited. Gaining insights into these aspects will be crucial in understanding the role of drusen and calcification in AMD progression and may expose opportunities for diagnostic and therapeutic interventions that will have a significant impact on public health, especially in the aging populations disproportionately affected by AMD. Therefore, I am employing a range of biophysical techniques, such as fluorescence microscopy, aggregation assays, and solid-state nuclear magnetic resonance methods to investigate the structural, chemical, and physical properties of these calcified deposits. I am aiming to elucidate the mechanism of assembly of drusen, as well as structurally investigate the protein-mineral interactions within drusen.  

Evan Wen

Suzanne Enos

Molecular insights into Asp/Glu transport by the Mitochondrial Carrier Family

In humans, tight regulation of aspartate and glutamate concentrations in the mitochondria and cytosol is maintained by the aspartate/glutamate carriers (AGCs) of the inner mitochondrial membrane, also known as SLC25A12 (AGC1/aralar) and SLC25A13 (AGC2/citrin) – regulation that is critical for the citric acid cycle, gluconeogenesis, myelin synthesis in neurons, and neurotransmission. Through structural characterization by cryogenic electron microscopy (cryoEM) and complementary biochemical study, I aim to elucidate the transport mechanism, substrate specificity, and regulation of AGC1 and AGC2.

Lydia Chambers

Email: lychambers@ucsd.edu
Undergrad Institution: Gonzaga University
Current Program at UC San Diego: Biochemistry and Biophysics
Advisor: Kevin Corbett and Elizabeth Komives

 Bacterial antiviral defense pathways encode eukaryotic-like ubiquitination systems