Research Highlights
Toxic ‘forever chemicals’ are everywhere. Can you actually avoid PFAS? 4 strategies from experts
The Environmental Protection Agency created the first-ever limits on toxic “forever chemicals,” aka PFAS, in tap water. But there are steps to take now to reduce your exposure. PTPI T32 Trainee Darline Castro-Melendez in the Scheible Lab supplies some of this expert advice in articles featured in USA Today and the Today Show. The article takes the reader through the new national limits imposed by the EPA, what PFAS are and what they are used for, how we are exposed and the health effects, and strategies to avoid them.
One of the articles can be found here.
Thank you, Darline, for your part in getting this information to the public!
Immunology T32 trainees present at 2023 Microbiology and Immunology Retreat
Four current trainees presented posters this year at the annual departmental retreat for the Department of Microbiology and Immunology. In addition, two trainees also gave oral presentations on behalf of their labs.
Amelia Knudsen-Clark presented a poster entitled “An Acidic Microenvironment Disrupts Circadian Control of Macrophage Function”.
Alicia Healey presented a poster entitled “Aryl hydrocarbon receptor activation alters monocytic cell responses during coronavirus and influenza A virus infection”.
Tara Vrooman presented a poster entitled “A Combinatorial Approach to Provide Long-lasting Immunity Against Pancreatic Tumor Recurrence”. Tara also gave an oral presentation on behalf of the Gerber Lab!
Sophia Eliseeva presented a poster entitled “IFN-gamma induced microglial reprogramming”. Sophia also gave an oral presentation on behalf of the Yarovinsky Lab!
Great job to everyone, and thank you for your contributions to our T32 program and department!
Cooper Sailer publishes first-author paper in Frontiers in Immunology
Cooper Sailer published a first-author paper entitled “PD-1Hi CAR-T cells provide superior protection against solid tumors”
Chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising treatment option for several hematologic cancers. However, efforts to achieve the same level of therapeutic success in solid tumors have largely failed mainly due to CAR-T cell exhaustion and poor persistence at the tumor site. Although immunosuppression mediated by augmented programmed cell death protein-1 (PD-1) expression has been proposed to cause CAR-T cell hypofunction and limited clinical efficacy, little is known about the underlying mechanisms and immunological consequences of PD-1 expression on CAR-T cells. With flow cytometry analyses and in vitro and in vivo anti-cancer T cell function assays, we found that both manufactured murine and human CAR-T cell products displayed phenotypic signs of T cell exhaustion and heterogeneous expression levels of PD-1. Unexpectedly, PD-1high CAR-T cells outperformed PD-1low CAR-T cells in multiple T cell functions both in vitro and in vivo. Despite the achievement of superior persistence at the tumor site in vivo, adoptive transfer of PD-1high CAR-T cells alone failed to control tumor growth. Instead, a PD-1 blockade combination therapy significantly delayed tumor progression in mice infused with PD-1high CAR-T cells. Therefore, our data demonstrate that robust T cell activation during the ex vivo CAR-T cell manufacturing process generates a PD-1high CAR-T cell subset with improved persistence and enhanced anti-cancer functions. However, these cells may be vulnerable to the immunosuppressive microenvironment and require combination with PD-1 inhibition to maximize therapeutic functions in solid tumors.
The article can be found here. Great work, Cooper!
Mary Moran Receives Master’s Degree in Public Health
Mary Moran completed the MPH program within the Department of Public Health Sciences this past December. Mary joined the MPH program in the fall of 2020. This past semester, Mary worked with her PhD mentor, Dr. Lisa Beck, and her MPH mentor, Dr. Chris Seplaki on her final MPH project. Mary's project utilized a large biorepository and logistic regression models to investigate the association between history of S. aureus skin infections and history of the serious viral skin complication, eczema herpeticum, in subjects with atopic dermatitis. This project was funded by a grant Mary received from the National Eczema Association.
Poster Presentation by Cooper Sailer at Recent Conference
Cooper Sailer, a 5th year Cell Biology of Disease PhD candidate in Dr. Minsoo Kim’s lab, recently attended the American Association for Cancer Researcher (AACR) Tumor Immunology and Immunotherapy conference in Boston, MA. Cooper presented a poster on his research project titled “PD-1High CAR T cells exhibit superior effector functions in solid tumors". The conference brought together basic cancer immunologists and clinical oncologists to exchange ideas and to develop new approaches to treating cancer and improving patient outcomes.
The conference poster presentation was a nice opportunity to learn about the exciting research being done by colleagues in the field and allowed for great discussion about Cooper’s research project!
Alicia Healey presents at the AHR Symposium 2022
Alicia Healey, a 5th year Immunology PhD candidate in Dr. Paige Lawrence’s lab and T32 trainee, recently attended the Aryl Hydrocarbon Receptor (AHR) Symposium 2022 in State College, PA. Alicia presented a poster on her research project titled “AHR activation alters monocytic cell responses during coronavirus and influenza A virus infection". This symposium is aimed at bringing together researchers from across the AHR field to present their most recent findings, ranging from immunologists to biochemists to cancer biologists. Alicia was able to gain valuable feedback on her research from experts in the AHR field and connect with other trainees who share a similar research interest. Her favorite part of the symposium was a scheduled open discussion at the symposium that opened the floor to attendees to discuss the future of the AHR field. The topics/ideas that were brought up at this informal discussion were some of the most interesting and gripping ideas that Alicia had heard throughout the symposium!
Alicia received an MBI Seminar Travel Award which supported her attendance at this conference.
Mary Moran publishes research in JID Innovations
Mary Moran co-authored a manuscript detailing how different commonly used and commercially available keratinocyte culture media result in significant differences in a number of standard keratinocyte assays. This project was born out of the supply chain disruptions which resulted in the usual media used by the lab being back ordered. In an attempt to keep projects in the lab moving, other culture media were used, but it quickly became clear that depending on the culture media used, the cells would behave quite differently. This paper highlights how important it is for researchers to clearly state in their methods what reagents are used, as this may contribute to some variability in assay outcomes among labs. The manuscript titled “Supply Chain Disruptions During COVID-19 Pandemic Uncover Differences in Keratinocyte Culture Media” was published in JID Innovations.
Taylor Uccello Defends Thesis
Taylor successfully defended her dissertation on June 3, 2022, earning her a PhD in Microbiology and Immunology. Taylor's work in the Gerber Lab largely focused on developing an orthotopic mouse model of rectal cancer and using this model to explore the anti-tumor immune response generated following radiation therapy. Taylor's work identified an important immune signaling pathway that is necessary for a positive response to therapy. By targeting and enhancing this pathway directly, Taylor was able to improve the responsiveness to radiation therapy, which may translate to the clinic as currently only a fraction of rectal cancer patients treated with radiotherapy will respond to treatment.
Taylor will continue studying anti-cancer therapies during her postdoctoral position in Boston, MA.
Congratulations Taylor, we wish you the best in your next position!
Mary Moran presents at the SID Annual Meeting
Mary Moran recently traveled to Portland, OR for the Society for Investigative Dermatology (SID) Annual Meeting. Mary presented her project titled “Importance of CD40 Expression on S. aureus Superantigen Responses in Human Keratinocytes” during the Innate Immunity, Microbiology and Microbiome poster session.
Mary was also nominated by the Department of Dermatology and selected to participate in the SID Future Leaders Retreat. This retreat is for PhD students, pot-docs, medical students and residents whose research or specialty is focused on dermatology. This retreat kicked off the conference and included panel discussions on perseverance, developing a scientific program, navigating the appointments and promotion process, funding mechanisms, and publishing manuscripts. There were also small group discussions on entrepreneurship, industry, clinical trials, and academia. This was a great opportunity for networking with leaders in dermatology research.
Mary received an MBI Abstract Travel Award which supported her attendance at this conference.
Great work Mary!
Andy Martin presents at the AAI Annual Meeting
Andy Martin recently attended the American Association of Immunologist’s annual Immunology 2022 conference in Portland, OR. Thanks to both the T32 training grant in Immunology as well as the AAI travel award, Andy was able to present his work titled “Selective Reprogramming of Peritoneal Macrophages by IFN-𝛾 During Acute Toxoplasma gondii Infection” as both a podium and poster talk in the Immunity to Microbial, Parasitic, and Fungal Infections sessions I and II, respectively. Andy was able to get feedback on his work from a diverse audience of both experts and trainees with different cellular, model, and biochemical expertise as well as various different experiences and viewpoints. Andy’s favorite part of the conference was attending the talks given by other PhD students, as he got to see their work, progress, and enthusiasm. Following the talks he was able to connect with other students and talk about their projects, institutions, struggles, accomplishments, and plans for the future after graduation! Andy enjoyed this conference because it made him feel welcomed and connected to the field of immunology and he was able to learn about all the career opportunities, pitfalls to avoid, and members of this great community and field!
Great job Andy!
Chantelle White publishes a first-author paper in Viruses
Chantelle Lehone White published a first author paper entitled “A New Master Donor Virus for the Development of Live-Attenuated Influenza B Virus Vaccines.”
Influenza viruses continue to be a cause of global concern, resulting in 12,000 to 52,000 deaths annually in the US alone. At present, our best mechanism of protection is through annual vaccination. There are several licensed vaccine configurations, including both protein-based and live attenuated platforms. Live attenuated influenza vaccines (LAIV) allow for limited viral replication without the progression into an active disease state. Increased temperature sensitivity is a key feature of an attenuated virus. The temperature gradually increases throughout the respiratory tract, being lowest within the upper airways (33°C) and highest within the lower lung (37°C). Restricting viral replication to 33°C prevents active infection within the lower lung while simultaneously allowing the host to generate adaptive immune responses that target the entire virus. This is in contrast to protein-based influenza vaccines that are largely enriched for HA proteins alone. Over the past few years, there has been a notable decline in LAIV efficacy. It is important to note that even though the HA and NA components of the LAIV are updated annually, the backbone viruses utilized to express these surface proteins remain unchanged. The B/Victoria component of these quadrivalent LAIVs is still B/AnnArbor/1/1966. Overtime, the conserved viral proteins retained within these backbone viruses have accrued several mutations, leading to a significant decline in percent identity between the backbone virus and more recently circulating strains. In this paper, she introduced key mutations within a more recently circulating strain, B/Brisbane/60/2008, resulting in a highly temperature-sensitive phenotype. Using a mouse model, she confirmed that viral replication was restricted the nasal turbinates. She also performed challenge studies that confirmed the establishment of protective immunity. The increased identity between B/Brisbane/60/2008 and recently circulating influenza viruses of the B/Victoria lineage, as well as the observed immunogenicity, suggests that updating the current B/Victoria backbone virus will result in increased LAIV efficacy.
The article can be found here.
Chantelle White publishes research in Pathogens
Chantelle Lehone White was a contributing author on a recent publication in Pathogens entitled “Development of a Mouse Model to Explore CD4 T cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection.”
Influenza A viruses have been extensively studied in the literature but there has been very limited exploration into adaptive immune responses elicited upon influenza B infection. Here they used a mouse model to explore key features of B/Brisbane/60/2008-specific CD4 T cell responses. They show comparable replication kinetics in vivo. However, when assessing epitope specific responses, they found that B/Brisbane elicits a broadly reactive CD4 T cell repertoire while the A/California-specific CD4 T cell repertoire is more narrow, focusing on key immunodominant epitopes. B/Brisbane-reactive CD4 T cells were found within the mediastinal lymph mode and spleen. They were also readily detected within the lung, though they were enriched in the parenchyma relative to the vasculature. Together these studies provide insight into key features of influenza B infection and subsequent CD4 T cell responses and localization.
The article can be found here.
Mary Moran presents at American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting
Mary Moran recently traveled to Phoenix, AZ for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting. Mary presented her project titled “S. aureus Superantigens Found on AD Skin Alter Human Keratinocyte Biology” in a 10-minute oral presentation during the “Best of Allergic Skin Disease 2022 Oral Abstract Session”.
Mary’s research explores how S. aureus superantigens alter the epithelium to enhance susceptibility to viral infection. This is important in patients with atopic dermatitis (AD), who have high colonization of S. aureus on their skin and are also susceptible to a number of AD-specific viral complications. In addition to presenting her research, Mary was able to network with many scientists in the field of AD, including individuals' part of the collaborative Atopic Dermatitis Research Network, which helps support Mary’s research.
Mary received a AAAAI PhD Travel Scholarship and a travel grant from the University of Rochester Graduate Women in Science (GWIS) which supported her attendance at this conference.
Great work Mary!
Taylor Uccello published in Advances in Radiation Oncology
Taylor Uccello, a fifth year graduate student and T32 Trainee, has recently published an article in Advances in Radiation Oncology. The article is titled, "Development of an Orthotopic Murine Model of Rectal Cancer in Conjunction with Targeted Short Course Radiation Therapy". Taylor's work describes the establishment of a pre-clinical mouse model of rectal cancer that can be precisely targeted for radiotherapy. The work eloquently details the biological effects that radiation has on the tumor microenvironment. The article can be found here: https://www.advancesradonc.org/article/S2452-1094(21)00225-6/fulltext#seccesectitle0019
Immunology PhD candidate, Mary Moran, awarded Engagement Research Grant from the National Eczema Association
Mary Moran, a 5th year Immunology PhD candidate in Dr. Lisa Beck’s lab was awarded a one-year, $5,000 Engagement Research Grant from the National Eczema Association for her proposal titled “Importance of S. aureus virulence factors and barrier disruption in the extreme phenotype of eczema herpeticum". Mary will be utilizing a biorepository of serum and skin swab samples from patients will atopic dermatitis (AD) with and without a history of eczema herpeticum to measure a serum biomarker of barrier dysfunction (LDH) and quantify S. aureus virulence factors from skin swabs. Her research will assess correlations between barrier dysfunction, virulence factors, and viral infection. This research has the potential to identify factors that may identify patients who are at risk for developing eczema herpeticum, which may help clinicians proactively treat this AD subgroup.
Congratulations Mary!
Andrew Martin shares his experience as a PhD candidate with undergraduates at MCLA
On Friday November 12th, Andy Martin gave a talk to biology majors at his undergraduate institution, the Massachusetts College of Liberal Arts (MCLA). The seminar outlined what to consider when applying to graduate school and the myriad opportunities he made for himself or took advantage of while at MCLA. He explained how to get involved in undergraduate research, summer research experiences for undergraduates (REUs), mentoring/volunteering opportunities, and how to develop and utilize a professional network. Additionally, he presented some of his own graduate research conducted at the U of R, and how it related to his interests discovered through classes and opportunities he explored at MCLA.
Great job inspiring the next generation of graduate students Andrew!
Mary Moran and University of Rochester Science Policy Initiative (UR SPI) Memo Team awarded Honorable Mention in National Science Policy Memo Competition
A team of UR graduate students, Katherine Andersh, Zanah Francis, Mary Moran, and Emily Quarato, were awarded Honorable Mention in the Journal of Science Policy & Governance and National Science Policy Network International Science Policy Memo Competition. This competition was centered around the theme of intersectional science policy with a focus on issues related to justice, equity, diversity and inclusion in science. Their memo titled Period Poverty: A risk factor for people who menstruate in STEM has been published in the Journal of Science Policy & Governance. Their memo highlights how period poverty - the inability to access and afford menstrual hygiene products, contributes to school absences and places menstruators at a disadvantage in STEM education and careers, and advocates for instituting a requirement that all public K-12 schools provide free menstrual hygiene products to students. The team also placed first in the UR SPI Policy Memo Competition this past August.
Congratulations, Mary!
Immunology PhD candidate, Cassandra Houser, awarded F31 pre-doctoral fellowship from NIEHS
Cassandra Houser, a 4th year Immunology PhD candidate in Dr. B Paige Lawrence’s lab, was awarded an F31 predoctoral fellowship from the National Institute of Environmental Health Sciences (NIEHS). F31 fellowships supported by the NIEHS are expected to focus on the environmental health sciences. This initiative seeks to enable promising predoctoral students to obtain individualized, mentored research training from outstanding faculty sponsors while conducting dissertation research in scientific health-related fields that are relevant to the NIEHS mission.
Cassandra’s fellowship will focus on determining how the aryl hydrocarbon receptor (AHR), an environmental sensing transcription factor widely expressed within the immune system, regulates humoral immunity during respiratory viral infection.
Congratulations, Cassandra!
Andrew Martin is advancing his career with the AAI Advanced Course in Immunology
Each year, the American Association of Immunologists (AAI) offers advanced courses in immunology that incorporate 25 lectures, live panel discussions, and breakout sections to learn and share perspectives on a range of immunological topics. Attendees need a firm understanding of the basic principles of immunology and laboratory techniques to participate in the course successfully.
“I am registered for and planning to expand my knowledge of immunology through the AAI Advanced Course in Immunology. This course is set up to update and expand on my current knowledge in the field of immunology by interacting with a diverse selection of students/researchers. Many of my immunology peers have had great things to say about the course in the past when they took it. I hope to meet and develop connections with not only the world-renowned immunologists presenting recent advances in the field, but also the students that are attending from different backgrounds and institutions.”
Good luck, Andrew!
Andrea Amitrano publishes a first-author paper and accepts a postdoctoral position at Roswell Park Cancer Center
Andrea Amitrano is a 5th year Pathology PhD candidate in the lab of Dr. Minsoo Kim. Andrea recently published her first, first-author paper titled, Optical Control of CD8+ T Cell Metabolism and Effector Functions in Frontiers of Immunology. In addition, Andrea accepted a postdoctoral position in the lab of Dr. Scott Abram’s at Roswell Park Cancer Center in Buffalo, NY.
Great work, Andrea!
Amitrano AM, Berry BJ, Lim K, Kim KD, Waugh RE, Wojtovich AP, Kim M. Optical Control of CD8+ T Cell Metabolism and Effector Functions. Frontiers in Immunology, 2021. Doi: 10.3389/fimmu.2021.66623
Meet our 2020-2021 Trainees: Why we came to graduate school and our future plans
Andrea Amitrano: I decided to attend graduate school because I really enjoyed my research experience during my undergraduate studies. Attending graduate school has allowed me to further develop my skills as a scientist and as a critical thinker. After I complete my PhD, I plan to pursue a career in translational cancer biology research.
Cassandra Houser: I decided to pursue a PhD because I was fascinated by the science and enjoyed exchanging novel ideas with other people around me. Looking forward, I want to apply my scientific knowledge and skills in a way that positively impacts human health. I want to help discover new avenues of research that will lead to new therapies for those burdened by disease and preventative treatments for those healthy individuals that are at risk.
Andy Martin: During my undergraduate education, I discovered a passion for research and for teaching. To pursue these interests, I joined the University of Rochester as a Master’s student where I got a feel for high-level research and met a wealth of knowledgeable and friendly peers and faculty members. Once I received my Master’s, I knew I wanted to continue my quest for knowledge and receive a PhD here at the University of Rochester. Upon receiving my PhD, I would like to “return to my roots” by teaching at a small public liberal arts college. I hope to inspire budding researchers (or even non-science majors) to pursue their interests and develop a passion for research as they contemplate going to graduate school themselves.
Chantelle White: Prior to joining graduate school, I worked for several years in the clinical research setting. While I initially chose this position for the clinical experience, it was ultimately the research side of my position that captivated me the most. There came a point where the questions I was hoping to address went beyond the confines of my position. I ultimately chose to pursue graduate school because I knew that the extensive hands-on training and intellectual investment would provide me the tools needed to seek the answers to my own questions. I hope to pursue a career in biodefense research, focusing on vaccine development and antiviral treatments against emerging pathogens.
Taylor Uccello: I decided to attend graduate school because of my experience working in an immunology lab during my undergraduate studies. It was during this time that I realized how much I enjoy bench work and designing experiments. Once I finish my PhD work, I plan to continue to pursue a career in tumor immunology, with a strong focus on mentoring students.
Mary C. Moran: I decided to attend graduate school because I really enjoyed the research experiences that I had as an undergraduate and wanted to continue conducting research, learning new skills, and collaborating with other scientists. In addition to the Immunology PhD program, I am also enrolled in the MPH program. By pursing both of these degrees I will leave the University of Rochester with comprehensive training in bench-top and clinical research methods of infectious disease and an understanding of the epidemiology and public health policy that is required to address these diseases.
Research Spotlight
Taylor Uccello presents research at the International Conference on Immunotherapy Radiotherapy Combinations 5th Annual Meeting
Taylor Uccello recently traveled to Paris, France for the International Conference on Immunotherapy Radiotherapy Combinations 5th Annual Meeting (September 14th – 17th). Taylor presented a poster titled, “The Irradiation Effect on the Neuronal- Immune Axis in Rectal Cancer”. Taylor’s work explores how radiation therapy unintentionally influences the sympathetic nervous system. Adrenergic nerves have been shown to be highly immunosuppressive and hinder the anti-tumor immune response. Her research has determined that radiation therapy, alongside its many anti-tumor and immunostimulatory effects, induces neurogenesis and subsequent norepinephrine secretion. Taylor hypothesizes that this neuronal axis may contribute to the immunosuppressive arm of radiation therapy, and that if the neuronal signaling could be reversed, the efficacy of radiation therapy could be enhanced.
Great work, Taylor!
Taylor Uccello is awarded at the GWIS "Mentoring-Up New Year's Resolution Challenge"
Outlining and achieving goals is reliant on surrounding yourself with excellent mentors. The "Mentoring -Up New Year's Resolution Challenge" was sponsored by GWIS that asked students to set 3 personal and professional goals for the semester. Taylor partook in the challenge and wrote a report on her goals, how she would achieve them, and what mentors would help her along the way.
"My three professional goals were to improve my writing for my manuscript by attending the UR writing retreats, take ownership in developing my career goals by using the Individual Development Plan (IDP) tool, and expanding my scientific network, which was altered slightly by the pandemic, so I joined the cancer biology leadership group to set myself up to meet new people in the future..."
Taylor was 1 of 4 students selected to present at the GWIS meeting on May 20th, 2021 and she was awarded $1500 that could be used on an technology related items for her research.
Congratulations, Taylor!
Thesis Defense-Andrea Amitrano, PhD Candidate in Pathology
Andrea Amitrano is a PhD candidate in pathology in the PhD program in Pathology-Cell Biology of Disease at URMC. She is mentored by Dr. Minsoo Kim in the Department of Microbiology & Immunology. Now in the fifth year of her PhD program, Andrea will be defending her thesis titled, Optical Control of CD8+ T cell Metabolism and Effector Functions this year. Andrea’s thesis committee members are: Andrew Wojtovich, Paige Lawrence, and Yi-Fen Lee and her chair, Patrick Murphy. Andrea is also completing revisions on a first author paper.
Great work, Andrea!
SARS-COV-2 Research Published in the Journal of Infectious Diseases
Chantelle White is a second year PhD student in immunology in the Immunology, Microbiology, and Virology PhD program. Her advisor is Dr. Andrea Sant in the Department of Microbiology & Immunology. Since the emergence of the SARS-COV-2 pandemic, Chantelle has been focusing on the functional potential of circulating seasonal Human Coronavirus (sHCoV) - reactive CD4 T cells and she is author on a paper published on the subject this year titled, Circulating CD4+ T cells Elicited by Endemic Coronaviruses Display Vast Disparities in Abundance and Functional Potential Linked to Antigen Specificity and Age. Studies from her lab show that individuals unexposed to SARS-COV-2 have pre-existing, circulating sHCoV-specific CD4+ T cells that are cross-reactive with the SARS-COV-2 spike, nucleocapsid, and membrane/envelope proteins. Together, these studies provide an intriguing first look at the sHCoV-reactive CD4 T cell repertoire that a given healthy adult may possess before and ultimately carry into their fight against SARS-CoV2 infection. Additional studies will be required to further characterize how previous exposures to endemic sHCoVs shape the memory CD4 T cell repertoire and how the presence of these cross-reactive CD4 T cells may contribute to SARS-COV-2 disease outcomes. Chantelle will be expanding on these studies in her future dissertation research.
Amazing work, Chantelle! Take a look at the SARS-COV-2 paper published by the Sant lab!
Cassandra Houser Selected as Student Representative for SOT
Cassandra Houser, a fourth year immunology student in Dr. Paige Lawrence’s laboratory, was recently selected as the Graduate Student Representative for the Immunotoxicology Specialty Section of the Society of Toxicology (SOT). This position entails working with the Immunotoxicology Specially Section (ITSS) Executive Committee to organize ITSS alumni and networking events at annual SOT meetings. Cassandra will also be in charge of organizing and putting together the ITSS newsletter each quarter. In addition, Cassandra was also selected to give a poster presentation on her work studying the Aryl Hydrocarbon Receptor (AHR) in T follicular helper cells at the SOT annual meeting at the end of this month.
Congratulations Cassandra!
Tumor Metabolism and the Microenvironment Keystone Conference
T32 Trainee Andrea Amitrano was selected to give a presentation at this year’s Tumor Metabolism and the Microenvironment Keystone conference held virtually from January 25-28, 2021. Her presentation is titled “Regulation of CD8+ T cell Metabolism and Migration with Optogenetics”.
A summary of her presentation is as follows. “While cancer immunotherapy is effective against hematologic malignancies, it is ineffective against solid tumors due in part to significant metabolic challenges present in the tumor microenvironment (TME), where infiltrated CD8+ T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T cell recruitment to the tumor site and hypo-responsive effector functions via T cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8+ T cell activation, effector functions, and persistence in tumors. We found that the mitochondrial membrane potential is closely correlated with Granzyme B and IFN-y production. Additionally, activated CD8+ T cells migrating on ICAM-1 and CXCL12 coated wells consumed significantly more oxygen than stationary CD8+ T cells and inhibition of mitochondrial respiration decreases the velocity of CD8+ T cell migration, indicating the importance of mitochondrial metabolism in CD8+ T cell migration. Remote optical stimulation of CD8+ T cells that express our newly developed “OptoMito-On” successfully enhanced mitochondrial ATP production and improved overall CD8+ T cell migration, as well as effector functions. Our study provides new insight into the impact of the mitochondrial membrane potential on CD8+ T cell effector functions and demonstrates the development of a novel optogenetic technique to remotely control T cell metabolism and effector functions at the target tumor site with outstanding specificity and temporospatial resolution.”
Congratulations, Andrea!
Microbiology and Immunology Peer Mentor Award
T32 Appointee and 4th year graduate student, Taylor Uccello, was this year’s recipient of the Microbiology and Immunology Peer Mentor Award. This departmental award was established in 2015 and is awarded annually to a student nominated by their peers. Taylor works in Dr. Scott Gerber’s lab and has been a mentor to both visiting international students and undergraduates for the past 3 years. During this time Taylor has shown that she has a strong passion for teaching and mentoring, assisting students with developing their own projects and learning the lab techniques necessary to acquire a good foundation in research in immunology and cancer. Taylor also assists beyond the work in lab to assist students in applications for further education; two of the students that she has recently mentored have gone on to postgraduate education and medical school in their home countries. A huge portion of Taylor’s graduate school experience and interest in scientific research, she reports, can be attributed to having phenomenal mentors and learning the value and importance in mentoring others.
Research Published in Nature Immunology
Figure 3a – Neutrophils and monocytes/macrophages interactions in HKx31 influenza infected trachea of live mice on various days post infection.
Research Assistant Professor Dr. Kihong Lim from Dr. Minsoo Kim’s laboratory recently published an article in Nature Immunology titled, “In situ neutrophil efferocytosis shapes T cell immunity to influenza infection”. T32 appointee Andrea Amitrano and IMV graduate Dr. Alissa Trzeciak were contributing authors on this September 2020 publication. The paper explored neutrophil motility and interactions with resident phagocytes in vivo using impressive intravital multiphoton microscopy on influenza infected mouse airways. The authors determined that during the resolution phase, apoptotic neutrophils promote monocyte differentiation through epidermal growth factor secretion. Monocyte differentiation subsequently results in the emergence of a pool of tissue resident antigen presenting cells characteristic of CD103+ Dendritic cells (DCs). These neutrophil experienced, differentiating inflammatory monocytes (DCs) were shown to form stable immunological synapses with CD8+ T cells in the mouse trachea for prolonged periods of time in an MHC class I dependent manner. This suggests that neutrophil experienced inflammatory monocytes are performing an important APC function to activate anti-viral T cells and promote potent effector functions. Please take a look at the exciting results from their paper.
Microsphere Delivery of Immunotherapy Agents to Tumors
Booyeon Han (Linehan and Gerber Labs) publishes her work on the delivery of microsphere-encapsulated immunomodulatory agents to the tumor microenvironment. Using a model of pancreatic ductal adenocarcinoma, Booyeon found that within hours of intratumoral delivery, microspheres containing IL-12 were found in the tumor, lymphatics, and draining lymph node. The drainage of IL-12 microspheres from the tumor to the lymph node boosted Th1 cells and induced an antitumor cytokine profile that was essential for treatment efficacy. This efficacy was abrogated with draining lymph node ablation as noted by continued tumor growth and decreased survival. These studies demonstrate the potential for microsphere delivery of factors that locally modulate both tumor and lymph node microenvironments to enhance antitumor activity.
URMC Research Awards
Maureen Banach: Melville A. Hare Award for excellence in Research
Maxime Jean: Melville A. Hare Award for excellence in Research
Zanah Francis: Melville A. Hare Award for excellence in Teaching
Janelle Veazey: Outstanding Student Mentor Award
Poster Awards
Best Department Seminar - 2019
Jonathan Pinney - 3rd year
Science Policy Memo Writing Contest (3 prizes all to IMV students) – 2019
- Janelle Veazey
- Nicholas Battaglia
Recent Student Papers:
- Alissa Trzeciak
Title: Long-Term Microgliosis Driven by Acute Systemic Inflammation
Authors: Trzeciak, A, Yelena, VL, Kim, TH, Kim, MR, Mai, N, Marc, WH and Kim, M
Journal: Journal of Immunology
Links: Cover Images, Top Reads
- Daphne Pariser
Title: The Little Platelet That Could: PF4’s Regulation of Immune Responses.
Authors: Pariser, DN, Hilt, ZT, Bennett, JA, Morrell, CN
Journal: ASHI Quarterly
- Jonathan Pinney
Journal: Journal of Cell Science paper
*Waiting on response about paper acceptance
Funding
Daphne Pariser
- Vascular Discovery: From Genes to Medicine Travel Award for Young Investigators, Council of Atherosclerosis, Thrombosis, and Vascular Biology, 2019
- National Heart, Lung, And Blood Institute of the National Institutes of Health F31, NIH, 2019-2021, 1F31HL147458-01
Janelle Veazey
National Heart, Lung, And Blood Institute of the National Institutes of Health F31, NIH, 2018-2020, 1F31HL140795
Briaunna Minor
National Institutes of Health F31CA254132, “Double Duty: Elucidating the Effects of Estrogen on Tumor Cells and their Microenvironment in Lymphangioleiomyomatosis”
Project Summary: Lymphangioleiomyomatosis (LAM), a destructive cystic lung disease caused by TSC2-null, estrogen-sensitive, metastatic tumors, has a notable female sexual dimorphism and limited therapeutic options. Succinctly, the project is designed to delineate the mechanisms of estrogen actions in a murine model for Lymphangioleiomyomatosis (LAM) tumor growth, focusing on direct estrogen stimulation of TSC2-null LAM cells as well as estrogen involvement in the actions of granulocytic cells that infiltrate and promote LAM tumors.
Travel to Conferences
- Abstracts by Nick Battaglia, Cassandra Houser, and Janelle Veazey were selected for short talks at the 2019 Upstate New York Immunology Conference.
- A little about the conference by Janelle Veazey: “The Upstate Immunology conference is one of my favorites. It's a great chance to have lunch/dinner with the invited speakers including the keynotes! This year they also ran a mock study section, which was helpful to see what parts of your grant reviewers look at and discuss as well as better understand how [grant] scoring works.”