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Dominic has been in and out of hospitals his entire life. His artwork focuses on personal interactions with the healthcare system and his experiences dealing with chronic illness.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive cancer, with a mere 13% average 5-year survival rate. Conventional chemotherapy and immunotherapy regimens have limited effectiveness, and surgical resection of the tumor is not viable for the majority of PDAC patients diagnosed with advanced metastatic disease. Our previous research has shown therapeutic induction of cellular senescence with RAS pathway targeting therapies can induce cytokine and chemokine production through the senescence-associated secretory phenotype (SASP) that can effectively activate anti-tumor T cell immunity and responses to anti-PD-1 immune checkpoint blockade. To build on these findings and overcome limitations associated with senescence-inducing therapy toxicity, here we leveraged mRNA technology to deliver specific SASP cytokines and chemokines we have found to stimulate immune responses into the suppressive PDAC TME as an immune oncology platform. We created an in vitro transcription pipeline for mRNA production and have successfully demonstrated delivery of multiple mRNAs simultaneously into the TME of transplanted and autochthonous PDAC mouse models, stimulating the local production of cytokines normally absent in PDAC. We further characterized a novel combination of five cytokines and chemokines that can effectively recruit and activate both innate and adaptive immune responses against PDAC. Considering the recent success of off-the-shelf neoantigen mRNA vaccines in early human PDAC patient trials, we have now developed mRNAs that encode PDAC-specific antigens. By integrating our cytokine mRNA platform with antigen mRNAs, we observe a significant increase in intratumoral antigen-presenting dendritic cell populations, leading to substantially enhanced T-cell-mediated anti-tumor immune response. Long-term studies in autochthonous PDAC mouse models demonstrate that combining cytokine and antigen mRNAs can completely eradicate tumors in select cases, resulting in significantly extended survival. Overall, this study not only unveils pivotal insights into the cytokines absent in PDAC that are crucial for promoting anti-tumor immunity but also pioneers an innovative immunotherapy approach.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department quarterly newsletter for March 2025. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

Meet UMass Chan BMB Administrator III, Dr. Suresh Kannan!

Understanding how to fix the accessibility issues in the CMS that are noted in Siteimprove.

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Massachusetts is considering legislation called Primary Care for You (PC4YOU) that could have a national impact as the country deals with the challenges of access to primary care.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for December, 2024.

Meet UMass Chan BMB postdoc, Janneke Icso from the Kelch Lab!

Marlina Duncan, EdD, vice chancellor for diversity and inclusion, reminds the UMass Chan community that our diversity is central to our mission.

Transforming Chronic Pain Care: Insights from Dr. Sarah Pearson

Human T-cell leukemia virus type-1 (HTLV-1) is an oncogenic human retrovirus affecting over 20 million people worldwide. HTLV-1 infection can cause adult T-cell lymphoma (ATL) and other serious inflammatory diseases. Estimates report that 5-10% of HTLV-1 infected patients will develop a serious condition such as ATL, which has poor 4-year survival and high relapse rates. HTLV-1 has persistent infection rates across the globe and reaches up to 45% prevalence in certain communities. Despite this impact on human health, there are no direct-acting antivirals (DAAs) or vaccines against HTLV-1. HIV-1 and HTLV-1 are from the same viral family and encode for a homodimeric aspartyl protease crucial for cleavage of functional proteins from viral polyproteins. The activity of HIV-1 and HTLV-1 protease is essential to their viral life cycles. The Schiffer laboratory has extensive experience with viral protease crystallography and inhibition, especially with viral proteases for HIV-1, HCV NS3/4A, and SARS-CoV-2 main protease. This expertise uniquely positions me to design, synthesize, and characterize potent, resistance-thwarting protease inhibitors against HTLV-1 protease. Resistance-preventing DAA design is essential because of the selective pressure applied during DAA treatment. An ideal and proven strategy for developing a highly potent and resistance-preventing viral protease inhibitor is to target the active site through rational design using the substrate envelope. The substrate envelope for HTLV-1 protease has not been characterized and we lack a detailed understanding of the protease substrate specificity. I hypothesize that by translating strategies from our design of HIV-1 protease inhibitors, namely characterizing HTLV-1 protease’s substrate specificity, I can design potent and resistance-preventing DAAs for HTLV-1 protease. Aim 1: Characterize the structural basis for HTLV-1 protease substrate specificity. HTLV-1 protease cleaves six substrates by recognizing cleavage sites between individual proteins of the viral polyprotein. I will investigate the molecular basis of this recognition underlying protease specificity by determining cocrystal structures of the protease with bound substrates. The conserved volume inhabited by the substrates will define the substrate envelope and inform inhibitor design for HTLV-1 protease. Aim 2: Rationally design, synthesize, and characterize inhibitors of HTLV-1 protease to optimize potency. HIV-1 and HTLV-1 proteases share an active site amino acid sequence identity of 45% and high structural similarity. Therefore, I will begin inhibitor design by testing a selection of our in-house HIV-1 protease inhibitors, which have already shown low (1 µM) to moderate (30 nM) potency against HTLV-1 protease. I will combine experimental inhibition assays with cocrystal structure analysis to identify lead compounds for inhibitor design. I will leverage substrate specificity of the protease by moving inhibitor design towards compounds that mimic the shape of substrates, leveraging the substrate envelope (Aim 1), and the interactions between protease and substrate. I aim to produce novel, highly potent (sub-nM) inhibitors that will be promising DAAs for further investigation against HTLV-1.

Huntington’s Disease – a devastating neurodegenerative condition – is caused by a defect in the Huntingtin gene, resulting in the production of alternative forms of Huntingtin mRNA and protein. This proposal will use small RNA drugs to reduce alternative forms of Huntingtin in mouse models of Huntington’s disease and determine the effect on disease features and outcomes. Findings from these studies will provide insight into the mechanisms underlying Huntington’s Disease to inform the development of future therapeutics.

Mitochondria are essential for cell health and survival. Understanding the quality control machinery that mitochondria employ to maintain a healthy network is critical for health and disease. Our lab recently showed the role that lipid transfer protein Vps13D plays a critical role in mitochondrial clearance by autophagy (mitophagy) in the Drosophila developing midgut. Vps13D has been implicated in human movement disorders, highlighting the importance of understanding how it controls this process. Importantly, we do not know what proteins Vps13D may be interacting with at the mitochondrial surface to facilitate mitophagy. I performed an RNAi screen against mitochondrial genes that were shown to physically interact with Vps13D in human cells. I discovered that Mtch, the fly homolog of MTCH2, phenocopies both mitochondrial and autophagic defects that Vps13D mutants display, including failure to clear mitochondria, autophagic cargoes like p62, and the autophagy protein Atg8a. I generated a null mutant for Mtch, which displays phenotypes similar to what is observed by Mtch knockdown with RNAi and Vps13D mutants. Importantly, Mtch mutant cells exhibit a robust decrease in Vps13D protein puncta. I plan to use this Mtch mutant to: (1) characterize the function of Mtch in mitophagy, (2) determine the relationship between Mtch and Vps13D in mitophagy, and (3) investigate the relationship between Mtch and known regulators of autophagy and mitophagy. These studies will advance the field by creating a better understanding of mitophagy, and will also provide a novel genetic pathway to study that could lead to targeted therapies to correct mitochondrial disorders.

RNAi-based drugs are emerging as a new class of therapeutic modalities that are transforming pharmaceutical development. The National Institute of Arthritis and Musculoskeletal and Skin Diseases has granted a K99/R00 Pathway to Independence Award to Dr. Qi Tang to support his career transition to an independent principal investigator position at a U.S. academic institution and to fund his research on developing a programmable siRNA-based therapeutic platform for gene silencing in the skin. Dr. Tang will receive integrated scientific and career training during his K99 phase at UMass Chan, and in R00 phase, he will work to establish his independent laboratory with a focus on designing and expanding the utility of siRNA therapeutics for treating inflammatory skin diseases that currently lack sufficient treatments or are undruggable by conventional modalities.

Down syndrome (DS) is caused by trisomy for human chromosome 21 and affects more than five million individuals worldwide. Autism spectrum disorder (ASD) is a common co-occurring condition in persons with DS. Because individuals with DS-ASD often present with deleterious behaviours, such as self-injurious behaviour, aggression, sleep disturbances, and feeding difficulties, identifying effective treatments for the behavioural sequelae of DS-ASD has the potential to improve quality of life for individuals with DS and their caregivers. However, recent research has focused on diagnosing DS-ASD and describing its behavioural profile. The underlying molecular mechanisms that contribute to DS-ASD risk remain unexplored. Other DS-associated phenotypes likely result from dysregulation of the Sonic hedgehog (Shh) signalling pathway, which is a critical developmental pathway. Because Shh signalling is required for the differentiation of serotonergic neurons and because the serotonergic system is implicated in the pathogenesis of ASD, we hypothesized that disruption of Shh could result in behavioural phenotypes relevant to ASD. To address this hypothesis, we will perturb Shh signalling in developing zebrafish and assess serotonergic neuron morphology, overall brain structure, brain activity, and behaviour. How trisomy 21 contributes to misregulation of Shh also merits further study. Based on a previous screen of chromosome 21 genes, we selected HMGN1 as a likely regulator of Shh. We will overexpress HMGN1 and explore its effects on Shh signalling, serotonergic neurons, behaviour, gene expression, and epigenetic modifications. Successful completion of this project will lay the foundation for drug screens relevant to DS-ASD and cognition in larval zebrafish models.

Negative affect and stress experienced during alcohol abstinence can be a major factor contributing to relapse in alcohol use disorder, yet underlying neurobiological mechanisms remain ill-defined. Corticotropin-releasing factor (CRF)-expressing neurons in the bed nuclei of the stria terminalis (BNST) are involved in anxiety and stress responses, and they play a major role in the withdrawal. A subcommissural population of CRF neurons in the BNST (vBNSTCRF) is heavily innervated by hindbrain noradrenergic neurons that co-express prolactin releasing peptide (PrRP). Because these PrRP neurons are sensitive to both stress and interoceptive state, they are likely involved in the development of stress hypersensitivity following withdrawal. However, the role of PrRP neurons in alcohol-related behaviors has not been studied. I hypothesize that signaling of PrRP neurons to vBNST during acute ethanol withdrawal contributes to the development of negative affective behaviors, and that ethanol withdrawal potentiates vBNSTCRF responses to stress and PrRP neuronal activation. In the proposed project, mice will undergo chemogenetic silencing of PrRP+ neurons projecting to vBNST during acute ethanol withdrawal to examine the necessity of the circuit in the development of negative affective behaviors (Aim 1). Then, the influence of ethanol withdrawal on in vivo calcium responses of vBNSTCRF neurons to stress and chemogenetic activation of PrRP+ neurons will be explored using fiber photometry (Aim 2). Finally, monosynaptic tracing and whole brain imaging will be used to define additional brain regions innervating vBNSTCRF neurons that may be modulated concomitantly during ethanol withdrawal (Aim 3). The results of these studies will provide an improved understanding of neurobiological mechanisms impacting affective behavioral changes during ethanol abstinence. This project also provides a strong platform to expand and strengthen the trainee’s expertise in modern behavioral neuroscience approaches, including intersectional viral strategies for chemogenetic manipulation of neural circuits, observation of cell-type specific in vivo calcium signaling, and characterization of monosynaptic inputs to specific cell populations.

Regulation of innate immunological self-tolerance, or the ability of cells to discern “self” from “non-self” has long been studied in the periphery in autoimmune disorders, especially in the context of nucleic acids (NA). Understanding of self-tolerance in the central nervous system (CNS), however, has not been thoroughly investigated despite expression of these NA-sensing TLRs by microglia, the primary phagocyte of the CNS. Published data from our lab highlights that microglia retain untranslated RNA transcripts from engulfed myelin for days after phagocytosis in vitro and in human multiple sclerosis patients. Based on these data, I hypothesized that these retained transcripts could aberrantly activate endosomal TLRs. I, thus, induced primary demyelination in UNC93B1 -/- mice, which lack functional NA-sensing TLRs, and observed that these mice remyelinate more efficiently than wildtype. These data suggest that signaling of NA-sensing TLRs suppresses remyelination during demyelinating disease. Several exciting questions have now arisen, which I will tackle in this proposal: 1) Is myelin phagocytosis causing aberrant endosomal TLR signaling? 2) Are microglia the primary cell type driving this response? 3) Does a specific NA-sensing TLR hinder remyelination? I hypothesize that TLR7 is aberrantly signaling in response to engulfed myelin RNAs in microglia and suppressing remyelination. To address these questions, I have acquired powerful in vivo molecular genetic tools to manipulate UNC93B1 and endosomal TLR function. I will first identify molecular pathways that are changed in microglia in vitro in response to chronic myelin phagocytosis and test whether these molecules are UNC93B1-dependent (Aim 1a). I will then determine if the UNC93B1 dependent effects that I observed on remyelination are microglia-specific (Aim 1b). Lastly, I will identify the endosomal TLR underlying these UNC93B1 effects (Aim 2). I am now in a strong position to molecularly dissect the role of NA sensing TLRs in remyelination during demyelinating disease, which has high long-term therapeutic potential.

B cells are essential immune cells that protect the host from infections via antibody production. This requires B cells to acquire e9ector functions and di9erentiate from naïve into germinal centers, and eventually into antibody-secreting plasma cells. Cell- cell interactions underpinning e9ective B cell response have been extensively studied, yet, less focus has been placed on soluble factors involved in this process, notably, mechanistic insights into lipid production and sensing on B cell immunity is still lacking. To this end, I will characterize the role of the liver X-receptors (LXR), nuclear hormone receptors regulating cholesterol homeostasis, during a B cell response. I aim to understand, with the highest granularity, how B cells integrate intrinsic and extrinsic lipid metabolic cues. Using cutting edge approaches, including conditional and inducible murine knock-out models, dietary interventions, targeted epigenetic profiling, single-cell RNA sequencing (ScRNAseq), and spatial transcriptomic to 1) Investigate LXR requirements for germinal center B cell and plasma cell di9erentiation, proliferation and maintenance in both homeostasis, vaccination and infection, in di9erent tissues; 2) Elucidate the molecular mechanisms of LXR transcriptional activity and regulation in germinal centers and antibody-secreting plasma cells; and 3) Identify the natural LXR ligand(s) that specifically shape B cell responses. My research will help resolve with high granularity how lipid metabolite sensing tunes humoral immunity in steady state and inflammation. Furthermore, it will help better understand B cell immuno-metabolic circuits that are tuned by lipid metabolites and that might be leveraged to design harmacological interventions enhancing antibody-mediated immunity.

Current DNP student at UMass Chan Medical School shares why they decided to pursue nursing as a career.

In today’s rapidly evolving health care landscape, the demand for highly skilled and knowledgeable nursing professionals has never been greater. As health care systems become more complex, the practice of nursing is expanding, necessitating advanced education and leadership skills to meet these new challenges. Here’s why pursuing a Master of Science for nursing interprofessional leadership is becoming increasingly important for modern nurses.

he Diversity and Inclusion Office, in collaboration with the Latino Medical Student Association, the Society for the Advancement of Chicanos/Hispanics and Native Americans in Science and Happy Feet, is planning a vibrant celebration of Hispanic Heritage Month on Thursday, Oct. 10, from 6 to 9 p.m. in the Albert Sherman Center multipurpose room. The event will honor the rich traditions and contributions of the Latinx community through an exciting evening of salsa and bachata lessons, cultural games and activities that showcase the lively spirit of Latinx culture and reflect the resilience, resistance and strength of the Latinx community. In advance of the event, read one community member’s reflection on salsa music, below.

A longtime leader in emergency medicine, David E. Wilcox, MD, FACEP, is funding a new award that will support research in the specialty at UMass Chan Medical School, where he was a valued faculty member for more than 15 years.

For Mark Eastham, MD'82, the course to a fulfilling medical career took a somewhat unusual route. It was first set on a summer day in the waters off Cape Cod, after a preliminary stop at the Hyannis Port estate of a rather well-known Massachusetts family. Many years later, the Lowell native is funding a scholarship at UMass Chan Medical School to help aspiring physicians launch their own careers in medicine.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for September 2024. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

Leslie Shaff, MD’84, P'99, and Harvey Shaff, DMD, and their family, including David Shaff, MD’99, Heidi Shaff, MD’00, Eric Shaff, MBA, and Sharon Shaff, CPA, fund new scholarship.

This academic year, the Diversity and Inclusion Office will address the ways diversity, equity and inclusion and disability can positively intersect by focusing its speaker series, Centering the Margins, on the theme, “Advancing Accessibility and Inclusion in Health Care for People with Disabilities.” The series will kick off on Sept. 25 at noon online, with the topic “Going beyond the basics: Successful communication between health care professionals and patients who are deaf, late deafened or hard of hearing.” Members of the UMass Chan community are encouraged to attend.

Renata Silva, PhD

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Opioid overdose deaths and other substance-related mortality remain at an all-time high in the United States, and evidence suggests that mortality will continue to worsen without significant changes to the landscape of opioid use disorder (OUD) treatment. Overdose mortality is the leading cause of death in the first two weeks post-release due to a variety of factors including changes in drug tolerance during incarceration and volatility of the illicit drug supply, leading to a more than 100-fold increased risk of overdose death compared to the nonincarcerated population during this period. Despite advances in addiction health services and clinical addiction medicine, many people with OUD do not have access to healthcare or medications for opioid use disorder (MOUD) treatment, which remain the most effective treatment strategies to reduce OUD- related mortality. Correctional facilities such as jails are a critical healthcare access point for people with OUD who may not receive healthcare in other settings. However, MOUD treatment availability in jails is highly variable across the United States, leaving many people with OUD without access to evidence-based treatment while incarcerated. Implementation of MOUD treatment in jails is critical to improve accessibility of MOUD treatment and reduce OUD-related mortality in this vulnerable population. There is need for further research elucidating strategies that lead to successful and sustained implementation of MOUD in jails and other correctional settings. This proposal uses a mixed-methods approach to analyze implementation of MOUD from multiple perspectives. The proposal utilizes data from the Massachusetts Justice Community Opioid Innovation Network (MassJCOIN) study, a type 1 hybrid effectiveness-implementation study of MA Chapter 208, which established a pilot program to expand all FDA-approved forms of MOUD in MA county jails. Aim 1 will qualitatively assess organizational factors related to MOUD implementation in jails and post-release overdose risk through thematic analysis of interviews with jail staff and people who received MOUD while incarcerated in MA jails. Aim 2 will investigate the association between staff perspectives of MOUD and organizational factors such as staff training and readiness for change. Aim 3 will compare MOUD retention outcomes for people who screened positive for OUD while incarcerated between different types of MOUD treatment using the Public Health Data (PHD) Warehouse database created by the Massachusetts Department of Public Health. The proposed research and training plan will provide rigorous education in addiction health services research, which will be integrated with the robust clinical training of UMass Chan Medical School and supported through a multidisciplinary team of mentors with significant expertise in implementation science and OUD research in criminal-legal settings. This proposal will provide valuable insights into strategies that lead to effective and sustained MOUD treatment in jail settings with the goal of increasing accessibility to evidence-based MOUD treatment and reducing opioid-related mortality for people who experience incarceration.

Close to 65 million US adults have a behavioral health condition (BHC), including mental health and substance use disorders.2 Persons with BHCs have a greater burden of complex health conditions, unmet health-related social needs (HRSNs) such as nutrition insufficiency and housing insecurity, use more healthcare, and are more likely to die prematurely.2 Access to mental health, addiction treatment, primary care services, and connection to social services in the same location is uncommon, even though physical illness, unmet HRSNs, mental health disorders, and substance use disorders often co-occur.6 Fragmented care is associated with increased hospital and emergency department visits, higher complication rates, and higher episode costs.30,31 Medicaid is the primary health insurance program for underserved populations in the United States. The main objectives of many recent Medicaid behavioral health-related policy reforms have been to integrate behavioral health treatment with primary care and to connect Medicaid members with social services in primary care settings.2,4,5 6,7,8 In 2018, Massachusetts’ Medicaid program, MassHealth, launched a new Accountable Care Organization (ACO) delivery and payment system to deliver integrated person-centered care to meet members’ social, behavioral, and physical health needs by integrating care within and between healthcare and social service sectors. MassHealth’s shift to this integrated ACO model attempts to provoke improved healthcare outcomes and decreases in acute and emergency healthcare utilization for Medicaid members, typically who have a higher prevalence of complex BHCs and HRSNs than the privately insured.2,4,5 13 In this study, we will examine the effects of healthcare and social service integration on the experiences and outcomes of MassHealth members with BHCs. We will first analyze data collected from qualitative interviews among a sample of 36 MassHealth members with BHCs to identify barriers and facilitators to good health, access to care, and effective care delivery, and to characterize their experiences with the integration of social, behavioral, and physical health supports.15,16,17-21 We will then conduct a cross-sectional analysis, using survey and MassHealth administrative data from 2022, to examine the relationship between primary care providers’ perceptions of clinical and social services integration, as measured on the Provider and Staff Perceptions of Integrated Care survey, and rates of acute and emergency healthcare utilization among MassHealth members with BHCs from the same clinics.22 Finally, we will use MassHealth administrative data collected between 2020 and 2022 to quantify the effect of receiving integrated housing supports through MassHealth’s Flexible Services Program on healthcare utilization among MassHealth members with BHCs experiencing housing insecurity or homelessness.

Tailored orientations like UMass Chan’s Inclusive Excellence Orientation, held for students historically underrepresented in medicine, are necessary because they remind students that they belong and gives them an opportunity to meet people who will be part of their network and sphere of influence.

Applying to nursing school can be an exciting and daunting process. Here are five tips to help you succeed in your nursing school application.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for August 2024. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings

Meet this month's feature, Joshua Pajak from the Kelch Lab in the BMB Department!

Join us (the BMB) in celebrating RNA Day by learning more about the innovative bioengineering by the Pederson Lab.

During this collaborative, she and her team worked with 10 community health centers to facilitate the implementation of a patient-centered approach to social needs screening. The approach, which they developed based on motivational interviewing, trauma-informed care, and stakeholder input, was called empathic inquiry.

Discussing Kim Kardashian's son's vitiligo diagnosis, dispelling myths, and raising awareness for a better future. Learn more and get support.

Vitiligo representation is growing in toys! Dolls, video games, and more now feature vitiligo. This promotes acceptance and understanding of vitiligo.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for July 2024. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

Learn why sun protection is vital for connective tissue disorders & get sun safety tips

Dermatomyositis explained: Muscle & skin disorder. Causes, treatments & living well.

Meet our feature of the month, research associate Hannah Brown of the Ryder Lab!

Pride is a vibrant and empowering celebration of diversity, inclusion and acceptance. However, we gather today at a time of both celebration and deep concern. While Pride serves as a powerful reminder of the LGBTQ+ community’s achievements and resilience, it also highlights the ongoing struggles they face

World Vitiligo Day, June 25th, is a day to raise awareness about the vitiligo, advocate for people with it, and foster a strong sense of community.

Vitiligo understanding & support. Learn about vitiligo & how to show support on World Vitiligo Day.

JAK inhibitors are a medications that show promise in treating vitiligo by interrupting the immune system signals that attack melanocytes.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for June, 2024. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

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Meet the feature of the month, Jessica Chrabasz! Jessica is a research associate in the Pryciak Lab and Massachusetts native. Find out more about the unique perspective she brings to the BMB department.

2024 Annual Lupus Symposium

The FDA recently announced the approval of Cosentyx for the treatment of hidradenitis suppurativa in adults

Recent Hidradenitis Suppurativa research suggests a potential new therapy in the fight against this condition using Botox

Hidradenitis Suppurativa (HS): Painful bumps, not acne. Learn about this condition & how to manage it.

Boston goes purple for World Vitiligo Day (June 25th, 2024)! Landmarks lit up to raise awareness for vitiligo.

Dr. Brian Kelch received the Education Service Award in 2024! Learn more about his dedication to education in this blog post.

By diving into the mechanistic underpinnings of alveolar soft part sarcoma (ASPS), Matthew Hemming, MD, PhD, and team revealed a targetable vulnerability ready for translation.

Breaking news! Dr. Celia Schiffer, the Chair and the Arthur F. and Helen P. Koskinas Professor of Biochemistry & Molecular Biotechnology, and the Director of the Institute for Drug Resistance, was elected to the National Academy of Sciences!

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for May, 2024. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

Meet Kathy Drolet, our wonderful department administrator!

Join us in celebrating the foundation of life as we know it by learning about innovative DNA-focused research in our department. Dr. Brian Kelch's lab is working to understand DNA-replication machinery across the tree of life in an effort to identify new candidate antibacterial targets.

The environmental justice movement began alongside the civil rights movement in the 1960s. Led by people of color, particularly Black people, the movement sought to bring attention to the lack of environmental protections in communities of color.

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“What is the greatest impact you have as a behavioral health clinician (BHC) on the primary care team?”

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for April, 2024. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

Deciphering the complex risk factors behind Autism Spectrum Disorder (ASD) is the passion of our own Dr. Summer Thyme at UMass Chan BMB.

Meet Leonard Barasa of the Thompson Lab at the UMass Chan BMB department. He is a brilliant chemist interested in developing new drugs to cure disease.

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With support from the UMass Cancer Pilot Grant Program, Lucio Castilla, PhD, is working on a way to deliver a targeted therapy for inversion(16) acute myeloid leukemia. he is collaborating with S. Thai Thuyamanavan, PhD, an expert in drug delivery, to develop an antibody-nanogel conjugate capable of delivering a small molecule to AML cells and kill them.

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Misgendering, the act of using incorrect pronouns, can have profound negative consequences. When someone is consistently referred to by pronouns that align with their gender identity, it conveys a sense of acceptance and belonging, fostering a safe and inclusive environment.

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Vitiligo research advances! UMass Chan's VCORT Symposium brings together experts for breakthroughs in treatment and cures.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for March, 2024. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

BMB department faculty members Dr. Francesca Massi & Dr. Celia Schiffer, alongside Dr. Jasna Fejzo at UMass AMherst, were awarded a grant from the Massachusetts Life Science Center to purchase a brand new NMR machine! Find out why this is a big deal and how it might change the face of scientific research at UMass Chan Medical School.

Meet Karen Welch, the Executive Assistant to the Chair in the Biochemistry & Molecular Biotechnology Department (BMB) at UMass Chan Medical School!

A cancer diagnosis impacts more than the patient. Timothy Sannes, PhD, tells us about how he helps patient caregivers as well.

Learn why the TP53 mutation in acute myeloid leukemia is particularly worrisome and what Shyam Patel, MD, PhD is doing about it.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for February, 2024. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

Meet PhD student Christopher Jahns in the Flores-Kim lab in the Biochemistry & Molecular Biotechnology Department (BMB) at UMass Chan Medical School!

Clinician burnout has become an alarming epidemic in healthcare, affecting up to 60% of clinicians (Shanafelt et al., 2015). This phenomenon is linked to increased rates of depression, anxiety, and substance use, as well as elevated errors and diminished quality of care. Various factors contribute to burnout, including systemic issues like escalating quality metrics, administrative burdens, and shorter patient visits.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for January, 2024. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

The overarching goal of this proposal is to gain a deeper understanding of oligodendrocyte progenitor cell (OPC) phagocytosis and determine how it compares to the phagocytic ability of microglia and its relevance for neurological disease. Oligodendrocyte progenitor cells (OPCs) are a pool of progenitors found in the adult brain that give rise to mature, myelinating oligodendrocytes throughout life. Recent work has established that OPCs function as phagocytes and engulf synapses within both the developing and adult brain. This challenges the long-held notion that the sole function of OPCs is to generate new oligodendrocytes and establishes a role for OPCs in synapse pruning, similar to microglia. However, there is currently no understanding of how OPC phagocytosis impacts their progenitor function or how their phagocytic function compares to microglia. It is also unknown if OPCs function as phagocytes in the context of neurodegeneration. I will now use a combination of in vitro and in vivo phagocytosis assays and live cell imaging to compare OPC and microglial phagocytosis under steady-state conditions and during neurodegeneration and determine how phagocytosis impacts OPC function as progenitor cells. In Aim 1, I will use in vitro phagocytosis assays coupled with live cell imaging, OPC differentiation analyses, and RNA-sequencing to compare microglia and OPC phagocytosis of synaptic substrates and determine how phagocytosis impacts OPC differentiation. In Aim 2, I will utilize an animal model relevant to multiple sclerosis (MS) where the Schafer lab has shown early synapse loss and AAV-driven inhibition of complement C3 deposition to determine if OPCs function as phagocytes in the context of neurodegeneration, and if this phagocytosis is complement C3-dependent. The proposed studies will build on emerging work that challenges the current thinking that microglia are the primary phagocytes of the CNS. It will reveal the role of OPC phagocytosis in modulating the differentiation capacity of OPCs. It will also determine if OPC phagocytosis is dependent on the deposition of the complement protein C3. These results will have implications for neurodegenerative diseases, as lack of OPC differentiation is observed in multiple neurodegenerative states. Additionally, complement is now a target for therapeutic intervention in a variety of neurological diseases, so understanding how this pathway regulates other cells of the brain is essential for the effective use of these therapeutics. Finally, the experiments outlined here combine my strength in OPC biology from graduate school with the expertise in microglia and mechanisms of phagocytosis in my postdoctoral lab. Together, these studies will give me ideal training to achieve my goal of becoming an independent researcher studying glia-glia interactions in neurodegeneration.

Physical frailty, characterized by decreased physiologic reserve and increased vulnerability to stressors, and cognitive impairment, ranging from mild impairment to dementia, often co-occur in older adults. Both are associated with considerable adverse health outcomes, high healthcare costs, and substantial caregiver burden, and highly prevalent in U.S. community-dwelling older adults. However, for older adults receiving long-term care in nursing homes, data is scarce on the prevalence of the two conditions over their stay. Community-based studies suggest heterogeneous clinical presentation of physical frailty, which may have implications for its management. It is unknown if such heterogeneity is similar in older nursing home residents and if it is influenced by cognitive impairment. Further, physical frailty and cognitive impairment share risk factors and predict future onset of one another but the mechanism of this complex interplay remains unclear. Lastly, depression is strongly correlated with both conditions, yet findings regarding the impact of antidepressants on the progression of physical frailty and cognitive impairment are inconsistent. This proposed F99/K00 project seeks to address these gaps by two specific aims with population longitudinal data and advanced statistical methods. Aim 1 (dissertation research) focuses on older nursing home residents and will describe the prevalence of physical frailty and cognitive impairment; identify subgroups of physical frailty and examine the variation of subgroups by cognitive impairment levels; and delineate the developmental trajectories of physical frailty and cognitive impairment and examine the correlations between trajectories. Aim 2 (post-doctoral research) expands to older adults in the community and will assess the reciprocal association between physical frailty and cognitive impairment; quantify the impact of cumulative exposure to antidepressants on trajectories of physical frailty, cognitive impairment and depressive symptoms; and examine the effect of depressive symptoms as a mediator of physical frailty on cognitive impairment with causal mediation analysis. Methodological innovations include the use of latent class analysis, group-based trajectory models, structural equation models (autoregressive cross-lagged panel analysis; autoregressive latent trajectory model), and causal mediation. This proposal is directly relevant to the growing aging population in the U.S., including those residing in the nursing homes and those living in the community, since it uses the national nursing home database Minimum Data Set 3.0 (Aim 1) and the nationally-representative Health and Retirement Study linked to Medicare Part D Drug Event Files and the Harmonized Cognitive Assessment Protocol (Aim 2). This project will shed light on the concurrent progression of age-related physical and cognitive conditions. Results will inform future work to develop diagnostic tools and prediction models to facilitate timely identification of older adults at risk for accelerated functional decline, and implement care tailored to older adults’ needs to effectively delay the onset of negative health outcomes, enhance quality of life, and foster a healthy longevity.

The Biochemistry & Molecular Biotechnology (BMB) department celebrated the holidays with a lively festivus / holiday party that included the airing of grievances.

The Biochemistry & Molecular Biotechnology (BMB) department organized an event at the American Society of Cell Biology Cell Bio 2023 Meeting called "Science Art Relaxation Hour." Conference attendees had a chance to decompress by creating scientific art. This outreach event within the scientific community created opportunities for scientists to network and benefit from the relaxing influence of art. This was co-organized by Dr. Haley Barlow and Dr. Leonora Martinez-Nunez.

Certain viruses in the picornaviridae family, specifically enterovirus-D68 (EV68), have emerged as global health concerns over the last decade with severe symptomatic infections with EV68 able to result in long lasting neurological deficits and death. There are currently no US Food and Drug Administration approved drugs for any non-polio enterovirus, highlighting the need to develop strategies against these lethal enteroviral strains. One particularly attractive class of potential drugs are small molecules inhibitors, which can act as direct-acting antiviral (DAA) inhibitors towards the conserved active site of EV68 3C protease. This main viral protease is a cysteine protease conserved in the 3C family, responsible for cleaving eight sites along the viral polyprotein, which is essential for viral propagation. DAAs designed to target 3C proteases can potentially achieve robust inhibition across enterovirus species. However, as drug resistance in viruses can be prevalent, it is paramount to design inhibitors less susceptible to resistance mutations. It was demonstrated previously in the Schiffer Lab that when bound to protease, viral substrates occupy a conserved three-dimensional volume called the substrate envelope. It was also demonstrated that inhibitors that extend beyond the substrate envelope are more susceptible to drug resistance mutations. By utilizing the substrate envelope and cocrystal structures of the proteases, DAAs designed to fit within the three-dimensional consensus volume as naturally occurring substrates will interact primarily with functionally important residues and be less susceptible to drug resistance mutations. The central hypothesis of this proposal is that cocrystallization of EV68 3C protease with its natural substrates will enable the calculation of the substrate envelope to inform on substrate specificity, which will also aid in the design of robust pan-3C-protease inhibitors. In Aim 1, I will determine the cocrystal structures of EV68 3C protease bound to viral substrates. I will then use these structures to elucidate the molecular mechanism of substrate specificity for EV68 3C protease and calculate the substrate envelope. These data will aid in small- molecule design to create DAAs with improved resilience to mutations that can confer drug resistance. In Aim 2, I will design and test novel DAAs that target EV68 3C protease. I will first characterize previously designed inhibitors for other 3C and 3C-like proteases with the substrate envelope to establish a starting compound based on potency. Inhibitors based on the scaffold will be designed, synthesized, and tested in a FRET-based enzyme inhibition assay. Crystallization of novel potent compounds with EV68 3C and their characterization within the substrate envelope will assess inhibitors’ susceptibility to drug resistance mutations. Overall, this study aims to develop a robust, novel compounds with resistance-thwarting protease inhibition against the emerging pathogen that is EV68.

UMass Chan offers multiple opportunities to engage in service in honor of Martin Luther King Jr.

The Biochemistry & Molecular Biotechnology (BMB) department collaborated with the Worcester Public Library to exhibit a collection of scientific images & illustrations by our scientists. This was a hugely successful science outreach and community engagement effort organized by Dr. Leonora Martinez-Nunez.

The Biochemistry & Molecular Biotechnology (BMB) department organized an event at the American Society of Cell Biology Cell Bio 2023 Meeting called "Science Art Relaxation Hour." Conference attendees had a chance to decompress by creating scientific art, which is shown in this Instagram reel. This outreach event within the scientific community created opportunities for scientists to network and benefit from the relaxing influence of art. This was co-organized by Dr. Haley Barlow and Dr. Leonora Martinez-Nunez.

UMass Chan Biochemistry and Molecular Biotechnology (BMB) Department newsletter for December, 2023. The newsletter includes a list of new hires, upcoming events and seminars, information about this month's Anti-Racism Reading Club, department news, a link to the feature of the month, recent blog posts, a list of recent publications, wellness tips, and departmental job openings.

Pipeline Programs aid in diversity, equity, inclusion and antiracism

This newsletter was created by our Diversity and Inclusion Office to serve as a platform for the often-unheard voices of individuals living in the margins whose stories are integral to our shared human experience and align with the values and mission of our institution. In this special issue, we seek to do just that by focusing on a story of great breadth and timeliness: the crisis in Israel and Palestine. Through the powerful voices of our community, we aim to shed light on the diverse and nuanced ways individuals within our community have been shaped and transformed because of this long and ongoing crisis.

John Harris, MD, PhD, and team are using their UMass BRIDGE funds to perfect their self-delivering drug that enhances the immune system in melanoma. They are optimizing the drug to ensure durability, efficacy and efficiency to help bring the drug forward to clinical trials.

For the fifth consecutive year the UMass Cancer Research Office received commendations from ECOG-ACRIN. To top it off, this year they received FULL commendation for the first time!

Dohoon Kim, PhD, and team are poisoning cancer cells from the inside. With the help of a UMass Chan Bridge Fund, they aim to develop a drug that blocks a detoxifying enzyme from neutralizing a dangerous metabolite within cancer cells. Without this detoxifying enzyme, the cancer cells will die.