Amgen Scholars

Justin is a rising senior at UCLA majoring in Molecular, Cell, and Developmental Biology. Justin started in the Spencer Lab in the summer of 2022. There, Justin studies the influence of macrophage-specific Spp1 on the dystrophic phenotype and cell-cell interactions in the dystrophic muscle niche. This is all with the aim of better understanding Duchenne Muscular Dystrophy (DMD) and the mechanisms that increase its severity.

Duchenne muscular dystrophy (DMD) is an inherited degenerative muscular disorder caused by mutations in the DMD gene. Mutations in the DMD gene cause a loss of function of dystrophin, a protein essential for muscle cell membrane integrity via the dystrophin-glycoprotein complex (DGC). As a result, muscle cells are prone to chronic injury, dysregulated inflammation, and fibrosis. As an Amgen scholar, Justin will study DMD using muscular dystrophy X-linked mice (mdx mice), which are mice with a dystrophic background because of a point mutation in the DMD gene that causes them to express non-function dystrophin. This model will be used alongside the macrophage conditional knockout mouse line (MϕcKO) created by the Spencer Lab. The ablation of macrophage osteopontin has led to the disappearance of two stromal cell subclusters. The two subclusters were transcriptionally characterized and found to be novel stromal cell populations, which the Spencer lab refers to as ApoD(+) and Cxcl13(+) stromal cells. Using immunofluorescence techniques, Justin will find out if macrophage osteopontin is responsible for the viability of these cells and through which mechanism this happens. Justin will also characterize the phenotypic effects of missing ApoD(+) and Cxcl13(+) stromal cells on the mdx mice muscles. The preliminary characterization will involve using intracellular fat staining to uncover any difference in the amount of intracellular fat in MϕcKO compared to the control mice.

Justin is exceptionally grateful to everyone at the Spencer Lab for their kindness, patience, and helpfulness. This is especially so for Justin’s graduate student mentor, Raquel Aragón, and his PI, Dr. Melissa Spencer. Justin would also like to thank the Amgen Foundation for this opportunity and their support in his journey to become a physician-scientist.

Zachary Caterer, an undergraduate student at the University of Wisconsin-Eau Claire (UWEC), is focused on the development and integration of novel imaging techniques, machine learning, and artificial intelligence to enhance diagnostic accuracy and improve point-of-care practices. At UWEC, he contributed to a project in the Department of Biomedical Engineering and Materials Science and Department of Computer Science, where he assisted in developing deep learning algorithms for automated and precise detection and classification of laser-based spectroscopic images. This advancement has the potential to revolutionize diagnostic processes, aiming to enhance patient treatment and outcomes.

As an Amgen Scholar, Zachary is currently working on integrating machine learning and fluorescence microscopy techniques to create an automated system for the accurate detection of Mycobacterium tuberculosis (Mtb) in patient smears. By utilizing environment-sensitive probes and the low-cost fluorescence microscope Octopi, his objective is to streamline the diagnostic process and improve the efficiency and reliability of TB detection. The project involves investigating optimal parameters for probe detection, distinguishing between live and dead cells, assessing drug resistance, and detecting Mtb cells in human samples. Through this research, Zachary aims to contribute to global efforts in combating tuberculosis and ultimately enhance patient care.

Zachary extends his sincere gratitude to the Amgen Foundation and The Kamariza Lab for the invaluable opportunity to develop and execute his project, further refining his skills as a researcher.

Arden is a rising senior chemistry major at Carleton College. He greatly values the time he spends with his peers exploring scientific understanding, and is particularly interested in physical and analytical chemistry and biochemistry and their applications in advancing society.

As part of the Amgen Scholars Program at UCLA, Arden is conducting research in the lab of Dr. José Rodríguez in the Department of Chemistry and Biochemistry. The Rodríguez lab studies structural biology with computational, biochemical, and biophysical approaches using imaging methods such as electron microscopy, x-ray diffraction, and electron diffraction. Arden is using these diffraction methods to explore structural aspects of binding in enzyme inhibition. Papain is a cysteine protease used as a model system for numerous analogous enzymes including the particularly relevant PLpro domain of Nsp3 from SARS-CoV-2, which is vital for viral replication. Inhibition of papain is possible with small molecules such as E64 that irreversibly bind the thiol group at the active site characteristic of these enzymes. Examining binding of E64 derivatives is of interest for selective inhibition of cysteine proteases, which has potential as a therapeutic tool in targeting viral and neurodegenerative disease pathways.

Arden would like to thank his mentors Professor Rodríguez and Niko Vlahakis for their invaluable guidance, as well as UCLA and the Amgen Scholars Program for providing him with this opportunity to grow as a scientist.

Christina is a rising senior at UCLA majoring in Molecular, Cell, and Developmental Biology. She has worked in Dr. Crosbie’s lab since December 2021, where she studies how the mechanotransduction protein YAP can alter inflammatory macrophage behavior in Duchenne muscular dystrophy (DMD), enhancing overall disease pathology.

DMD is a rare, X-linked disorder that currently has no cure and is ultimately fatal. Patients experience progressive muscle weakness and muscle degeneration, as well as chronic inflammation and muscle fibrosis due to elevated macrophage activity. Muscle fibrosis results in elevated extracellular matrix (ECM) stiffness, activating mechanosensing proteins such as YAP, which normally regulates cell proliferation, but also has a potential role in polarizing macrophages towards an inflammatory phenotype in stiffer environments. Christina’s project with the UCLA Amgen Scholars Program seeks to better understand how macrophage cytotoxic behavior is altered when YAP is activated in macrophages by the stiffer, fibrotic environment of DMD muscle. Using cytotoxicity assays and immunofluorescence techniques, Christina hopes to better understand mechanisms of immunomodulation and macrophage behavior in DMD.

Christina would like to thank her graduate student mentors, Pranav Kannan and Daniel Helzer, and Dr. Rachelle Crosbie for their incredible mentorship and support, as well as the Amgen Foundation for this amazing opportunity to continue her growth as a scientist.

Charlotte is a rising senior at Wesleyan University double majoring in Molecular Biology and
Biochemistry, and Neuroscience and Behavior. At Wesleyan, she works in Dr. MacQueen’s lab, using
budding yeast as a model organism for studying the dynamics of meiotic proteins involved in the structure
and function of the synaptonemal complex.
As a UCLA Amgen Scholar, Charlotte works in Dr. Askary’s lab in the Molecular, Cell and
Developmental Biology Department, and this lab focuses on creating and utilizing new or modified
molecular tools to understand embryonic development of the mammalian retina with the goal of using this
understanding to develop better therapeutic strategies and molecular diagnostics for neurodegenerative
disorders of the eye. Charlotte is using a modified single molecule fluorescent in situ hybridization
(smFISH) procedure developed by a member of the Askary Lab to visualize the presence and localization
of the expression of 33 different genes of RPCs in embryonic mouse tissue with the hopes to use this
combined spatial and transcriptional information to characterize subtypes of RPCs that could inform on
what biases an RPC to assume a certain cell fate. This would provide further insight into the development
of the retina, as well as a means of generating a reliable source of different retinal cell types to use for
studying treatment of retinal damage.
Charlotte would like to thank Dr. Askary, her mentor Pratiti Dasgupta, lab manager Yuka McGrath, and
the other members of the Askary Lab for their guidance, support, and encouragement, as well as the
Amgen Foundation for this amazing opportunity!

Miriam Lepiz is a rising senior at UC Irvine conducting research in the Rodriguez Verdugo lab in the Department of Ecology and Evolutionary Biology. Her project is focused on increasing the realism and diversity of a three-strain synthetic microbial community representative of the Loma Ridge site in Irvine Ca.

As a UCLA Amgen scholar, Miriam is conducting research in Dr. Hong Zhou’s lab in the Department of Microbiology, Immunology, and Molecular Genetics and the Electron Imaging Center for Nanomachines. The Zhou lab focuses on 3D structural studies of biological complexes using Cryo-EM and Cryo-ET.

For the summer, she has focused on constructing an atomic model of the Mammalian Reovirus (MRV) using a cryo-em map. MRV is a segmented dsRNA virus with two capsid layers, belonging to the Reovirdae family. It is known to be a gastrointestinal virus capable of infecting all mammals but has low pathogenicity towards humans. This virus is studied due to its oncolytic function and to be used as a model for more pathogenic viruses that belong to the Reovirdae family. An atomic model of MRV will provide a high enough resolution to study the interactions within the intermediate particles of the virus during viral replication and assembly.

Miriam would like to thank Dr. Hong Zhou and Dr. Xiaoyu Liu for their incredible mentorship and extensive support. She would also like to thank the Amgen Foundation for providing her with the opportunity to grow as a researcher.

Marcos Moliné is a rising third-year neurobiology student at UCSD, working in the Molina Lab at UCSD Health, where they study mitochondrial dysfunction and its relation to healthy aging.

As part of the UCLA Amgen Scholars program, Marcos is working in Dr. Richard Staba’s Lab. His project focuses on analyzing the effects of the potential drug treatments, deferiprone and levetiracetam, in preventing epileptogenesis after traumatic brain injury (TBI).

Because the onset of epilepsy can take months to years to occur in humans after TBI, Marcos’ project uses rats as an animal model. TBI is induced, and high frequency oscillations, interictal spikes, and seizures are monitored as biomarkers during the acute period (14 days) following TBI.  Currently, anti-seizure medications such as levetiracetam are prescribed to epileptic patients to treat their seizures. However, this drug only prevents symptoms. Therefore, there is a need for a treatment to prevent epileptogenesis after TBI, especially considering that 15-50% of patients who experience TBI develop epilepsy. Deferiprone has been identified as a possible anti-epileptogenic treatment because it is an iron chelator and will metabolize potentially harmful iron released in the brain due to bleeding. The lab hypothesizes that a combination of deferiprone and levetiracetam will reduce the observed biomarkers, indicating increased potential as an anti-epileptogenic treatment, which can be further studied in clinical trials.

Marcos is very grateful to Dr. Richard Staba and Dr. Cesar Santana-Gomez for their mentorship this summer, as well as to the Amgen Foundation and UCLA for giving him this opportunity.

Truman is a rising senior at the University of California, Santa Cruz (UCSC) who studies Molecular, Cellular, and Developmental (MCD) Biology. Since June 2022, he has been conducting undergraduate research in the Chamorro-Garcia lab of the Department of Microbiology and Environmental Toxicology at UCSC, where he has been studying the obesogenic effects that microfiber microplastics have on mesenchymal stem cells as they differentiate into adipocytes.

This summer, through the Amgen Scholars Program, Truman is working with the Farmer lab of the Department of MCD Biology at the University of California, Los Angeles, which studies the inter- and intracellular mechanisms that drive and disrupt craniofacial development. Truman is attempting to visualize the periosteal dura, a layer of the meningeal tissues that sits just below the calvaria of the skull. While it is understood that the meninges are integral to proper calvaria bone growth and function, it is unclear if the periosteal dura has a supporting role in this interaction. Truman and the Farmer lab hope that visualizing the periosteal dura throughout the stages of zebrafish development will elucidate the relationship the periosteal dura has between the calvaria and the rest of the meningeal tissues.

Truman would like to thank Dr. Farmer, Benny Mosquera, Katie Wilhem, and the Amgen Foundation for investing their time, energy, and resources in him and his summer research project. Their support has made for an unforgettable summer of scientific and self-discovery.

Alyssa is a rising senior at Cal Poly in San Luis Obispo studying Biochemistry. At Cal Poly, Alyssa works in Dr. Andres Martinez’s research laboratory and has been testing enzyme stabilizers on paper for applications on point-of-care (POC) microfluidic paper-based devices.

At UCLA, Alyssa is conducting research under Dr. Daniel T. Kamei in the Department of Bioengineering. The Kamei Laboratory focuses on the development of novel POC diagnostics and was the first to apply aqueous two-phase systems (ATPS) to lateral-flow immunoassays (LFAs). ATPSs can be used to pre-concentrate a target biomarker into a smaller volume to improve the sensitivity of LFAs. Previous studies done by the Kamei Laboratory have shown that polymer-salt ATPSs can decrease the LFA limit of detection by 10-fold. However, because polymer-polymer ATPSs are more temperature resistant than polymer-salt ATPSs, they are more applicable at the POC. Alyssa’s current project is to optimize the use of a polymer-polymer ATPS composed of polyethylene glycol and dextran for use with LFAs. Since dextran is too viscous to efficiently flow across a LFA, the enzyme dextranase will be used to cleave dextran into smaller subunits. This should improve the flow of dextran by decreasing viscosity and consequently, increase the sensitivity of the LFA.

Alyssa would like to thank Dr. Daniel Kamei, Frances Nicklen, and all of the members of the Kamei Laboratory for being so welcoming and helping her grow as a scientist. She would also like to thank the Amgen Foundation for funding this amazing summer research opportunity.

Originally from Tucson, AZ, Sean is a rising senior at Northwestern University studying biology with minors in Data Science and French. At Northwestern, Sean works in the lab of Dr. Thomas Hope, where he has highlighted trends in PET/CT and vaccine trial data to better understand the dynamics of HIV infection. He is passionate about science education, as well as finding ways to integrate computational biology work with the discovery of niche coffee shops in Chicago.

At UCLA, Sean is working in the Meyer lab to decipher complex immune cell relationships within and between patients with systemic lupus erythematosus (SLE). Single cell RNA sequencing (scRNA-seq) is used to profile heterogeneity in biological systems, but current analysis strategies lack the ability to robustly differentiate patient-to-patient variation when comparing samples across many different individuals. To profile multi-experiment scRNA-seq data, the Meyer lab has adapted PARAFAC2, a multidimensional variance decomposition method, to first align data between experiments and subsequently perform dimensionality reduction. PARAFAC2 enables a 3-dimensional approach to linear decompositions of scRNA-seq data, and is thus better able to model natural variation. This summer, Sean is applying this method to 1.2 million cells derived from 260 patients, with the goal of using PARAFAC2 to strengthen understanding of the cell-level changes that contribute to the SLE disease state.

Sean would like to thank Andrew Ramirez, Dr. Meyer, and the rest of the Meyer lab for their invaluable support throughout the summer, as well as the Amgen Scholars program at UCLA for this opportunity.

Aishini is a rising senior at UC Davis. There, she conducts research in the Ori-McKenney Lab on the phosphorylation of microtubule-associated protein tau following traumatic brain injury and has investigated the underlying dopaminergic and serotonergic neuronal activity in the development of tau pathology.

At UCLA, Aishini works under Dr. Anthony Covarrubias in the Department of Microbiology, Immunology, and Molecular Genetics to conduct research on cell cycle regulators p21 and p16 in senescent macrophages. Cellular senescence, a cell fate characterized by irreversible cell-cycle arrest in response to various stressors, is an emerging driver of aging and aging-associated diseases. The Covarrubias lab has identified macrophages as a new cell type that can undergo senescence. Subsequent tests performed by the lab indicate an increase in senescent marker p21 in senescent macrophages, but a decrease in senescent marker p16. Aishini’s project in the Covarrubias lab thus entails determining the role of p21 and p16 in the senescent programming of macrophages. She is using CRISPR/Cas9 genome editing to generate p16 and p21 knock-outs in primary macrophages. Then, following treatment with irradiation, which is known to induce senescence through DNA damage, she will conduct various assays on these cells to test the effects on senescent programming. She hypothesizes that p21, but not p16, is important for macrophage senescent programming, and overall aims to identify markers of cellular senescence in resident macrophages.

Aishini would like to thank the entire Covarrubias lab, especially Dr. Anthony Covarrubias and graduate student Grasiela Torres, and the Amgen Foundation for this opportunity to enhance her skills as a researcher.

Elise is a rising senior at Western Washington University, where she conducts undergraduate research in Dr. Jeanine Amacher’s structural biology and protein biochemistry lab. While in the Amacher lab, Elise has studied protein-peptide interactions in a variety of proteins/domains – including Sortase A enzymes, SH3 domains, and PDZ domains – and recently published a first-author journal article.

At UCLA, Elise works for Dr. Lily Wu in the Department of Molecular and Medical Pharmacology; her focus for the summer is to investigate the inhibitory effect of statins on triple-negative breast cancer (TNBC) cell lines. Statins are commonly used to lower blood cholesterol by inhibiting HMG CoA reductase but have been seen to pleiotropically inhibit a variety of aggressive cancer types, including TNBC. TNBC does not exhibit overexpression of human epidermal growth factor receptor 2 (HER2) and does not express estrogen or progesterone receptors (ER and PR). Two of the most common therapies for breast cancer are anti-HER2 and endocrine-based and are therefore not effective against TNBC. Statins present a possible therapeutic method for treating this type of cancer, but not much is currently known about the mechanism/pathways at play. This project aims to gain insight into the inhibitory action of statins in this context, particularly as it relates to epithelial-to-mesenchymal transition, metastasis, and hypoxia.

Elise is very thankful for this wonderful opportunity to work with everyone in the Wu lab and for the support of both the Amgen Foundation and UCLA.

Mark is a rising senior at Cal Poly, San Luis Obispo, where he conducts organic synthesis research in Dr. Scott Eagon’s medicinal chemistry lab. In the “E-Lab,” he attempts to synthesize small molecule benzoxazole inhibitors of casein kinase 2 (CK2), an understudied kinase that phosphorylates over 700 different residues and is known to be upregulated in numerous types of cancers.

This summer at UCLA, Mark works for Dr. Peter Clark in the Department of Molecular and Medical Pharmacology where his focus is on expressing Hexokinase 2 (HK2) and both identifying and characterizing potential small molecule inhibitors of it. Elevated glucose consumption via aerobic glycolysis—known as the Warburg Effect—is fundamental to nearly all cancers and hexokinase catalyzes the first rate-limiting step of glycolysis. Given this and the fact that HK1 and HK2 provide redundant protection from loss of function for either of these isoforms of hexokinase, the Clark Lab aims to selectively inhibit HK1^– HK2⁺ cancers (40 percent of hepatocellular carcinoma cases) by identifying small molecule inhibitors of HK2. Using enzymatic and thermal shift curve assays, Mark looks to better understand the mechanisms behind which small molecules identified from high-throughput screening inhibit HK2.

Mark would like to thank Dr. Clark and his mentor, Stefani Perez, as well as Ph.D. candidate K.M. Ryan and undergraduate Rachel Jiang for their wonderful mentorship and support. He would also like to thank UCLA and the Amgen Foundation for the opportunity to explore a different field of research this summer.

Matthew is a rising senior majoring in microbiology at Oregon State University. There, he works in Dr. Hannah Rowe’s lab where he studies interactions between the microbiome and influenza A virus that contribute to the stabilization and propagation of viral infections.

As an Amgen scholar at UCLA Matthew works in Dr. Lili Yang’s lab in the department of microbiology, immunology and molecular genetics. The Yang lab focuses on developing novel cancer immunotherapies by studying the mechanisms behind antitumor immunity. Matthew’s project specifically focuses on the effects of creatine supplementation on the cellular activation of dendritic cells within the energy-poor tumor microenvironment (TME). Previous research has shown that creatine is important for preventing an “exhausted state” in T-cells within the TME and that creatine supplementation results in decreased tumor growth in mouse melanoma models. However, the effects of creatine on other members of the tumor microenvironment is largely understudied. The goal of Matthew’s work in the Yang lab is to look for activation markers in non-treated, creatine supplemented and ATP supplemented dendritic cells in order to gain a better understanding of how creatine affects the cellular activation of dendritic cells and how it may play a role in disease detection and immune activation.

Alex is a rising senior at UCLA majoring in Neuroscience and Design | Media Arts. Since his sophomore year, he has been performing research with Dr. Sotiris Masmanidis’s Lab at UCLA to study the neural mechanisms involved in reward learning and movement.

During the UCLA Amgen Scholars Program, Alex is investigating the behavioral and electrophysiological characteristics of gait and locomotion in healthy and Parkinson-like model mice. Gait impairments are characteristic of cognitive decline and some neurodegenerative disorders such as Parkinson’s Disease (PD). PD pathology includes symptoms such as dopaminergic neuron death in neural circuits involving the basal ganglia and implicated in proper movement modulation. Preliminary data from the Masmanidis Lab has demonstrated basal ganglia neural encoding for limb gait parameters in healthy mice and disruption of such neural firing in neurotoxin Parkinson-like mice models. However, such neurotoxin models, such as induced dopaminergic neuron death with 6-hydroxydopamine, do not fully characterize PD pathology, such as development of misfolded α-synuclein aggregates including Lewy bodies and Lewy neurites. Using computational ethology for behavioral gait tracking and electrophysiological recordings of the basal ganglia, Alex is exploring gait in healthy mice and mice injected with pathological α-synuclein in the basal ganglia to quantify the behavioral and neurological deficits associated with PD.

Alex would like to thank the UCLA Amgen Scholars Program, the Amgen Foundation, and the Masmanidis Lab for the opportunity and their support in his growth as a researcher and scientist.

Jerry is a junior at Amherst College pursuing majors in Biochemistry and Economics. While at Amherst College, he conducted research with Professor Lara Halaoui, studying the effects of dopant rare-earth metals on the electrocatalysis of the oxygen evolution reaction for water splitting.

As an Amgen Scholar at UCLA, Jerry is working in Dr. Neil Harris’ lab in the department of neurosurgery. His project in the Harris lab involves a collaboration with the Dr. Ina Wanner lab to investigate neurodegeneration in brain cells following repetitive minor traumatic brain injuries (TBI) using immunofluorescence. There are many studies showing that moderate and severe TBI leads to changes in the brain’s pathology and cognition in both the short and long-term. However, recent findings suggest that repetitive minor TBI also has short and long-term effects. In the Harris lab, Jerry will undergo an explorative study to determine where and to quantify how much neurodegeneration is occurring in the brain following repeated minor TBI in the acute phase. He will do this by staining mouse brains with antibodies that detect neurodegeneration and imaging them. This study has great relevance to contact athletes who often encounter multiple mild brain traumas throughout a season of play. Furthermore, it will further research on the early detection of and cures for Alzheimer’s Disease.

Jerry would like to thank the Amgen Foundation, the Harris Lab, and the Wanner Lab for their extensive mentorship and generous support in his exploration into the world of science.

Alexis is a senior at the University of California, Irvine (UCI) majoring in Public Health Sciences. While at UCI, she conducted research in the Lee-Jang lab working on understanding the basics of kidney metabolism under different experimental conditions that emulate those of human diet patterns.

As a visiting Amgen Scholar at UCLA, Alexis is working in Dr. Michael Teitell’s lab in the Department of Pathology and Laboratory Medicine. Her project in the Teitell lab consists of understanding the effect that mitochondrial DNA (mtDNA) has on extracellular vesicle activity, specifically exosomes, in cancer. The lab has generated preliminary data showing a connection between mtDNA and exosome expression. However, there is no indication of how mtDNA defects may impact the progression of cancer downstream. The Teitell lab seeks to define this relationship by engineering cells with mtDNA mutations using a technique, MitoPunch, that was established internally. Once cells are engineered with the desired mutations, they can be selected for and metabolically characterized. The exosomes produced from these engineered cell lines can be isolated and their contents identified. The results obtained from the experiments conducted could allow for the development of new therapeutic agents that target exosome expression in cancer.

Alexis thanks the Amgen Foundation, the UCLA Amgen Scholars Program, and the members of the Teitell lab at UCLA for their mentorship and support.

Daria Azizad is an undergraduate Neuroscience student at the University of California, Los Angeles. She is particularly interested in studying molecular mechanisms and biological pathways in relation to human disease. In the Bhaduri Lab in the Department of Biological Chemistry, Daria primarily studies cortical organoid metabolism, glioblastoma invasion in the organoid system, and does bioinformatics projects to investigate cell type through RNA-seq and ATAC-seq data. 

As an Amgen Scholar, Daria is studying the influence of hormones on cortical cell fate specification and metabolism in the organoid system. The cortical organoid model system is an effective tool for the study of cortical development and related pathologies; it lacks many connections that the endogenous brain has, including interactions with the endocrine system. Therefore, the organoid model acts as a “blank slate” in which many factors found in vivo are not present. Thus, through selectively introducing factors to study their role, their function may be further elucidated. Daria’s project aims to better characterize the role of the hormones estradiol, progesterone, and T4 in early cortical development, with the overall goal of investigating the effects of the stated hormones on the metabolic profile, gene expression, morphology, and cell survival in the cortical organoid.

Daria would like to thank the Amgen Foundation and the Bhaduri Lab for the incredible opportunity to develop and execute her independent project and enhance her skills as a researcher.

Alvaro is a rising fourth-year Molecular, Cell and Developmental Biology Major at the University of California, Los Angeles. As an undergraduate, he worked in Dr. Julia Mack’s laboratory developing machine learning models for image segmentation and imaging calcium signaling activity in zebrafish embryos. The Mack Lab is interested in elucidating mechanisms of endothelial mechanotransduction in the context of vascular health and disease.

For the UCLA Amgen Scholars Program, Alvaro will be conducting research in the laboratory of Dr. David Nathanson in the Department of Molecular and Medical Pharmacology. The Nathanson Laboratory focuses on understanding the functional biology of brain cancer and the development of novel therapeutics to target glioblastoma, an aggressive and lethal malignant tumor. Aberrations in the signaling cascades of ErbB/HER family of tyrosine kinase receptors are a hallmark of several types of cancer; specifically, mutations in the EGFR/HER1 receptor can lead to uncontrolled cellular proliferation and migration. Therefore, this pathway presents itself as a target for therapeutics aiming to combat cancer growth. For his project, Alvaro will be investigating the selectivity and potency of a novel small molecule tyrosine kinase inhibitor against metastatic EGFR-driven non-small-cell lung cancer. This research could provide invaluable information for further inquires into the novel drug’s ability to target other EGFR-driven cancer types.

Alvaro would like to thank Dr. Nathanson and his graduate student mentor, Quincy Okobi, for all the support and an unforgettable summer. Alvaro would also like to thank the Amgen Foundation for this opportunity to conduct research during the summer.

Mai Dang is a rising junior at Pomona College. As an undergraduate, she conducts research in the Negritto lab, where she investigates factors Rad 4, Rad 3, and Rad 30 in budding yeast to elucidate their role in Non-Homologous End Joining, a major pathway for the repair of double-strand breaks.

At UCLA, Mai is working with Dr Daniel Kamei in the department of Bioengineering. The Kamei Lab works on improving Lateral-Flow Immunoassays, a point-of-care diagnostic device. They have previously pioneered a technique called ACE-LFA, in which Aqueous Two Phase Systems are exploited to pre-concentrate biomarkers by minimizing the volume of the phase into which the target partitions, increasing the LFA’s limit-of-detection. The Kamei Lab also uses the system to introduce colorimetric substrates that increase test & control line intensity. While exciting results have been obtained, the Kamei Lab would like to be able to theoretically predict the optimal signal enhancement reagent for a range of ATPS combinations. The Lab has therefore developed a thermodynamic model to predict signal enhancement reagent partitioning. The goal of Mai’s project is to evaluate the model by measuring the partition coefficients of two colorimetric substrates in two different ATPSs and comparing them with predicted values. Subsequently, she will investigate any correlation between enhancement reagent partitioning and ACE-LFA performance by running ACE-LFA trials with the four conditions.

Mai would like to thank the Amgen foundation, Dr Daniel Kamei, and all the members of the Kamei Lab for investing time and resources towards her growth as a researcher.

Cynthia is a rising third year at UC Santa Barbara majoring in Pharmacology. At UCSB, she works in Dr. Weimbs’ lab, where she studies the mechanism of polycystic kidney disease.

As a UCLA Amgen Scholar, Cynthia works in Dr. Crosbie’s lab in the Integrative Biology and Physiology department studying muscular dystrophy. Duchenne muscular dystrophy (DMD) is an X-linked childhood onset degenerative disease caused by loss of function mutations in the DMD gene that encodes for dystrophin, affecting 1 in 5700 males. Patients with DMD have muscle weakness, leading to loss of ambulation as well as respiratory and cardiac dysfunction, ultimately leading to death. Dr. Crosbie has identified a transmembrane protein, sarcospan (SSPN), that associates with major adhesion complexes that provide stability to the cell during muscle contraction. Overexpression of SSPN in dystrophin-deficient mdx mice (murine model of DMD), improved skeletal muscle pathology and cardiac physiology. Previous studies have taken a targeted approach to determine which proteins are important for SSPN to ameliorate dystrophic pathology in mdx mice. To identify the global molecular mechanisms underlying SSPN’s cardioprotective effect, the Crosbie lab performed proteomics analysis on 1-year old wild-type, mdx, and mdx^TG (transgenically overexpressing SSPN) hearts. Cynthia’s project will involve identifying the pathways of interest that could be contributing to the rescue of DMD by SSPN in cardiac tissue and to confirm the proteomics data by immunofluorescence analysis and western blots.

Cynthia would like to thank the Amgen Foundation, Dr. Crosbie, and mentor Hafsa Mamsa for supporting her interest in research.

Kate is a rising junior studying Biochemistry at Vassar College. There Kate studies the structure and character of plasmid protein orf-90 under the mentorship of Dr. Krystle McLaughlin. The McLaughlin lab investigates the role of plasmid proteins in conferring antibiotic resistance. As an AMGEN Scholar at UCLA, Kate is working in Dr. Varghese John’s lab. Her project examines compounds that inhibit PLpro, a main protease integral to SARS-CoV-2 replication. Protease inhibitors could be a crucial protective agent against SARS-CoV-2, as they could be administered to infected individuals. By diminishing viral replication, the protease inhibitors diminish the prevalence of severe SARS-CoV-2 symptoms, long term SARS-CoV-2 symptoms, and hospitalizations.

The John lab has identified two PLPro inhibitors: DDL-701 and DDL-715. Kate will measure the PLpro IC50 of these compounds to elucidate the proper dose. Subsequently, Kate will determine whether new chemical entities inhibit PLpro in a PLpro activity assay. These compounds will be derived from successful SARS-CoV-2 protease inhibitors, such as Paxlovid TM, DDL-701, and DDL-715. Employing Paxlovid TM with the most potent PLpro inhibitors may amplify the inhibition of viral replication. Kate will then examine the Phase 1 metabolism of DDL-701, DDL-715, and any other identified inhibitors. The results will help elucidate how the protease inhibitors are metabolized and the rate of this metabolism. Kate would like to thank Dr. Varghese John and Jesus Campagna for their invaluable support, as well as the Amgen Foundation for this opportunity.

Karl is a rising senior at UC Davis, majoring in Biochemistry and Molecular Biology. Since his sophomore year he has performed research in Dr. Wolf Heyer’s lab studying BRCA2, which is a tumor suppressor protein involved in homologous recombination.

As an Amgen Scholar at UCLA, he is working in the lab of Dr. Guillaume Chanfreau in the Department of Chemistry and Biochemistry studying a recently discovered hybrid mRNA-snoRNA (hmsnoRNA). SnoRNA on their own can be transcribed from DNA in 3 different ways: independent transcriptional units, polycistronic clusters, or within the introns of pre-mRNAs. When snoRNAs are transcribed via introns, splicing is an important step in the formation of mature snoRNAs. The Chanfreau lab discovered that when splicing is interrupted, it can lead to the development of hmsnoRNAs. HmsnoRNAs consists of the processed 5’ end of an unspliced mRNA with a mature snoRNA on the 3’ end. As a result of their 5’ mRNA-like structure, hmsnoRNAs are exported into the cytoplasm and degraded via the mRNA decay pathway. Karl’s project focuses on examining whether or not hmsnoRNA can be translated into proteins. His project will utilize Western blot to detect for a FLAG tag which is coded in the theoretical coding region of the hmsnoRNA transcript being used.

Karl would like to thank the UCLA Amgen Scholars program for this opportunity, and Dr. Guillaume Chanfreau, Dr. Michelle Gibbs, and his graduate student mentor Sam DeMario for their assistance and encouragement in fostering his growth as a scientist.

Noah is a rising senior at Brown University majoring in chemical physics. At Brown, Noah works in Professor Brenda Rubenstein’s research group, where he employs replica exchange molecular dynamics simulations to investigate the mechanism behind the gout-preventing properties of Proteoglycan 4.

As a UCLA Amgen Scholar, Noah works under Professor Kendall Houk in the department of Chemistry and Biochemistry. This summer, Noah and the Houk group are working in collaboration with Professor David Baker’s group at the University of Washington to design the first ever enzyme catalyst for tetrazine cycloaddition reactions, a class of bioorthogonal reactions whose utility in molecular imaging and other biomedical applications can benefit from an effective enzyme catalyst. Recently, the Baker group used their newly developed deep-learning based methods to design many protein scaffolds with cavities that could have the potential to become catalytic binding sites. Utilizing their designs as a starting point, Noah will employ rotamer interaction field docking to modify the cavities of these designs so that it can bind and stabilize the tetrazine cycloaddition reaction’s transition state, the structure of which he will obtain via density functional theory calculations. Then, he will use a Monte-Carlo-based sequence design protocol to modify the amino acid sequences around the catalytic cavities in order to ensure that the designs are not only enzymatically active, but also possess high folding stability.

Noah would like to thank Dr. Kendall Houk and Declan Evans for their extensive mentorship, as well as the Amgen Foundation for supporting this research project.

Sofia is a rising junior majoring in Neuroscience and minoring in Computer Science at Duke University. At Duke, she works in Dr. Gustavo Silva’s lab to study the mechanisms by which cells regulate their mitochondria in the face of oxidative stress, a harmful process which damages cellular biomolecules, fostering cell death, and contributes to neurodegeneration.

As a UCLA Amgen Scholar, Sofia is working in Dr. Lindsay De Biase’s lab, which focuses on understanding why and how microglial regional specialization affects basal ganglia neuronal function as well as the viability of these neurons in the face of aging and pathology. Microglia are involved in almost every important brain process, spanning from early development to aging and neurodegeneration, and are most well-known for their phagocytic role as the brain’s immune cells, clearing the brain of dying neurons, synapses, debris, protein aggregates, and pathogens. In the De Biase Lab, Sofia is working on an assay to accurately visualize and quantify the phagocytic abilities of microglia in acute brain sections of mice. Development of this assay will enable more robust analysis of microglial phagocytosis in a variety of contexts such as developmental circuit maturation and circuit breakdown during neurodegeneration.

Mina is a rising senior studying biology at the University of Pennsylvania. During her sophomore year, she worked remotely with Dr. Knoepfler from UC Davis and researched about stem cells and cell therapies. Throughout her junior year, she worked with cancer cells and proteins at Dr. Yang’s lab at UPenn.

As part of the Amgen Scholars Program at UCLA this summer, Mina is conducting research at Dr. April Pyle’s lab, which involves studying the differentiation process of human pluripotent stem cells into muscle stem cells as well as the regenerative nature of muscle stem cells, which can potentially serve as a treatment for diseases involving muscular dystrophy, such as Duchenne Muscular Dystrophy (DMD). Mina’s research question focuses on the maturation of skeletal muscle progenitor cells (SMPCs) into muscle stem cells within this differentiation process. Specifically, she is working to see if the addition of ligands, including androgen, estrogen, and glucocorticoids, to SMPCs will promote maturation towards the muscle stem cell stage.

Mina would like to thank the Amgen Scholars Program, the Pyle Lab, and her mentor Peggie for an amazing opportunity to further her research interests this summer.

Stephanie is a senior studying microbiology at the University of California – Riverside. At her home institution, Stephanie conducts research in Dr. Adler Dillman’s nematology lab. The Dillman lab investigates how insect hosts recognize/initiate an immune response to parasitic nematode invasion and how parasites evade/suppress host immunity. Stephanie studies bacterial-induced immune responses of Drosophila melanogaster CRISPR mutants to examine the potential immune functions of various enzymatic homologs of the lipid and eicosanoid synthesis pathways.

As a UCLA Amgen Scholar, Stephanie works in Dr. Peter Bradley’s parasitology lab in the Department of Microbiology, Immunology, & Molecular Genetics. The Bradley lab studies the molecular biology of the obligate intracellular parasite Toxoplasma gondii, focusing on the roles that secretory organelles play during host-cell invasion. T.gondii causes Toxoplasmosis, a severe infection that develops in immunocompromised or pregnant individuals via contaminated food and feline feces. Stephanie’s project investigates the roles of T.gondii aurora kinases, TgArk2 and TgArk3, in parasite cell division and centrosome function. She explored whether the localization of TgArk2 is altered in a TgArk3 knockout background and how the loss of both TgArk2 and TgArk3 affects parasite fitness. By utilizing CRISPR/Cas9, cloning, and immunofluorescence assays, the lab aims to better understand these kinases and the clues they may provide for developing new drugs targeting parasite-specific functions in T. gondii and other apicomplexan parasites.

Stephanie would like to thank the entire Bradley Lab, especially Dr. Bradley and Rebecca Pasquarelli, for their mentorship and the Amgen Foundation and UCLA Amgen Scholars Program for their generous support.

Elaine Nagahara is a rising senior at Johns Hopkins University majoring in materials science and engineering with a concentration in biomaterials. In Dr. Luo Gu’s Lab at Johns Hopkins, she tunes material properties such as stiffness and viscoelasticity in alginate hydrogels to study their effects on cell behavior.

At UCLA, Elaine is translating her research background to investigating how changes in biomaterial properties affect the response of immune cells. While biomaterials have a large variety of healthcare applications, their success depends on how the immune system reacts to them. Once biomaterials enter the body, they interact with a myriad of molecular signals and different immune cell types via their material properties that modify the local microenvironment. This summer, Elaine is specifically studying how the presence of cell-adhesion peptides and the type of crosslinker used in hydrogel microporous annealed particle (MAP) scaffolds affect the response of antigen-presenting immune cells. MAP scaffolds are a novel class of injectable biomaterials that support the
regeneration of damaged tissue by facilitating host cells to infiltrate and form healthy complex tissue networks. She will create the MAP scaffolds with different conditions via microfluidics before seeding them with macrophages and dendritic cells. She will quantify their response by measuring the amount of scaffold uptake with fluorescence microscopy. These findings are important in creating an immunomodulatory platform that can target specific immune responses to advance tissue regeneration and other future applications such as vaccine development.

Elaine would like to thank the Di Carlo Lab for enriching and supporting her research interests, and the Amgen Foundation for funding this opportunity

University of California, San Diego

Junior

Biochemistry

Faculty Mentor: Dr. Albert Lai

Angie Santos is a rising junior at UCSD majoring in biochemistry. There, she conducts research in the Olivier George Lab, an addiction research laboratory, investigating the behavioral and neurological components of addiction via single-cell whole-brain imaging (iDisco+).

As part of the UCLA Amgen Scholars program, Angie is in the Albert Lai Lab in the Department of Neurology. The Lai Lab investigates the use of epigenetic editing to improve the effectiveness of chemotherapy against glioblastomas, an aggressive form of primary brain cancer. Glioblastomas have the lowest survival rate compared to other brain tumor types and there’s currently no known cure. Such a poor prognosis emphasizes how necessary it is for the development of possible therapeutics to help treat glioblastoma patients. Angie’s summer project focuses on the validation of a potential gene therapy that could improve glioblastoma patient outcomes.

Angie would like to thank Dr. Albert Lai, Blaine Eldred, and the rest of the Lai Lab for their incredible support and mentorship throughout the program. She would also like to thank the Amgen Foundation for making her research experience at UCLA possible.

Sahana is a rising junior studying the structure and function of intrinsically disordered proteins (IDPs) using biophysical methods under Dr. Elisar Barbar at Oregon State University. There, her research project has focused on studying RNA interactions with the SARS-CoV-2 N protein linker region.

As an Amgen Scholar at UCLA, Sahana is conducting research under Dr. Joe Loo in the Departments of Chemistry and Biochemistry. Her research for the summer leverages top-down mass spectrometry to study the protein cytochrome c and its interaction with ATP. Cytochrome c, or cytc, is a soluble heme protein that plays an important role in the electron transport chain of the mitochondria. Cytc has an ATP-binding site of high affinity and specificity, which is highly conserved across different species. Previous biochemical and molecular dynamics simulations demonstrated that ATP can effectively stabilize protein structure and inhibit aggregation. Preliminary work in the Loo Lab has shown that bovine cytc was stabilized by nonspecific ATP binding but also promoted the formation of a cytc dimer at a certain concentration threshold, a novel discovery. The lab hopes to better characterize the binding between cytc and ATP and investigate if cytc dimerization is relevant in nature.

Sahana would like to thank Dr. Joe Loo, her graduate student mentor Jessie Le, and the rest of the Loo Lab for all of their guidance and support. She would also like to thank the Amgen Scholars Program at UCLA for this invaluable opportunity to grow as a scientist.

Priyanka is a rising third year student at Stanford University majoring in computer science. At UCLA, Priyanka is with the Meyer lab in the Department of Bioengineering. The Meyer lab applies experimental and computational strategies to measure, model, and therapeutically manipulate cell to cell interactions.

Priyanka’s project focuses on computational methods to improve system serology research, research that broadens our understanding of antibody-mediated protection by quantifying both the antigen-binding and Fc biophysical properties of antibodies. Previously, the lab has created a general model for predicting the interaction of Fc receptors with effector cells, incorporating multivalent, multi-receptor binding. The lab has also shown how coupled matrix-tensor factorization is promising in reducing the dimensionality of system serology data while still retaining the most important aspects of the data. A limitation of tensor factorization, however, is that it can only show linear relationships, whereas immune system complex coupling with receptors exhibits nonlinear behavior due to the varying biophysical properties of receptors, antibodies, and individual patient homeostasis. Therefore, there is a need to represent nonlinearity in reduction techniques to make more biologically relevant analyses and conclusions.

This summer, Priyanka is developing a novel tensor-based dimensionality reduction that incorporates a mechanistic binding model and reflects the biological properties of immune system complexes. By constructing decompositions from known antibody properties, she hopes to be able to reduce the scale of future studies by highlighting both redundant and novel measurements or properties that cannot be deciphered from current methods. Priyanka would like to thank the Meyer lab for their mentorship and support, and the Amgen foundation for giving her this opportunity.

Margot is a rising senior, majoring in Biochemistry and minoring in Mathematics, at Mount Holyoke College. There, they have worked in the lab of Dr. Kathryn McMenimen since September 2020, where they are performing a holistic screening of heat shock protein induction in response to tau aggregation in D. melanogaster in order to study how tauopathies disrupt the chaperone response.

As an Amgen Scholar at UCLA, Margot is working in the Bitan lab in the department of Neurology. This lab studies the abnormal self-association of proteins and their role in human diseases. Margot’s project focuses specifically on the role of brain-derived exosomes in the tau seeding process. Indeed, tauopathies are a major class of neurodegenerative diseases caused by the misfolding of tau protein. Interestingly, they do not progress randomly through the brain but rather via specific disease-dependent neural networks. It is believed that exosomes, a type of extracellular vesicle that play an integral role in cell-cell communication, can act as vehicles for the disease-associated proteins between cells in the central nervous system. As a result, Margot is using fluorescent microscopy and flow cytometry to investigate whether exosomes from different brain regions and cell types possess discrete tau seeding capabilities in order to gain a better understanding of the progression of these diseases.

Margot would like to thank the Bitan lab for their guidance and support, as well as the Amgen Foundation for providing them with this opportunity.

Cole is a rising senior at UCLA majoring in Molecular, Cell, and Developmental Biology.  He has worked in Dr. Volker Hartenstein’s lab since his junior year.  The Hartenstein Lab is primarily interested in central nervous system development in Drosophila melanogaster, but Cole’s project investigates the aging Drosophila blood-brain barrier (BBB).

The BBB of humans declines with age and is correlated with age-related onset of neurological diseases.  Furthermore, mammalian models have shown loss of BBB function as a contributing cause of such diseases, including Alzheimer’s disease.  Age-related changes to the Drosophila BBB are not understood, but if a decrease in function is observed, the plethora of genetic tools in Drosophila could identify causes of the decline, which may have homology to causes in mammals.  To determine whether a decrease in Drosophila BBB function occurs with age, Cole is investigating the permeability of the young adult and aged BBB using nanoinjected, intrahemolymph dextran.  A functional BBB is impermeable to dextran, but dysfunctional BBBs are not, allowing dextran permeability to indicate BBB function.  To better understand potential causes of any age-related loss of BBB function observed, Cole is performing immunofluorescence for septate junction proteins, which are responsible for the BBB’s impermeability, to gauge their expression levels. 

Cole would like to thank Dr. Volker Hartenstein, Amelia Hartenstein, and Dr. Ceazar Nave for the development of this project and their instruction on the protocols.  Cole also thanks the Amgen Foundation and Amgen Scholars Program at UCLA for this resourceful and engaging summer research opportunity.

Eva is a rising senior at the University of California, Los Angeles with a major in Microbiology, Immunology, and Molecular Genetics and a minor in Biomedical Research. She has been a part of Dr. David Nathanson’s lab since October 2019. During her time there, she assisted in the development of a patient-derived glioma xenograft library and transitioned to developing novel potent, brain-penetrant drugs against glioblastoma.

Glioblastoma (GBM) is the most aggressive of primary tumors of the brain with a median survival time of less than fifteen months and no available cure, in part due to its extensive molecular heterogeneity. This heterogeneity makes it difficult to classify GBM into clinically relevant subtypes. However, recent studies have outlined a cell lineage-based stratification for GBM, in which a subtype of GBM may be dependent on human epidermal growth factor receptor 2 (HER2). Currently available HER2 inhibitors are unable to efficiently cross the blood brain barrier to inhibit brain tumors. Thus, the goal of Nathanson Lab is to produce a potent HER2 inhibitor that is also highly brain penetrant. To work towards this goal, Eva is characterizing drug potency and selectivity through IC50 assays and western blots in HER2-dependent cell lines, as well as brain penetrance through pharmacokinetics.

Eva would like to thank the members of the Nathanson Lab for their mentorship and supporting her growth as a scientist. She would also like to thank the Amgen Foundation and Biomedical Research Minor for their guidance and providing an opportunity to focus on her research.