Mendez Mentors

Our group is currently engaged in multiple studies investigating the young oral tongue squamous cell carcinoma. Projects that are appropriate for a 1 year research rotation include: 1) investigation of dietary exposures in non-smoking oral cavity cancer using 2 large cohort studies, the Nurses' Health Study and the Health Professionals' Follow-Up Study. We will be analyzing the microbiome in available biospecimens. 2) Comparison of Fusobacterium-dominance (>1%) in oral cavity cancer responders and non-responders to immunotherapy, 3) Investigation of a blood biomarker as a surrogate for Fusobacterium-dominant OSCC. These studies are currently initiated or ongoing and the student would play and integral role in data and tissue collection, data analysis, and manuscript preparation. There is an expectation and opportunity to present results at a national conference. There is an opportunity for formal research training which is provided by our existing T32 training grant infrastructure. There is also opportunity to enrol in a Biomedical Statistics course, which most of our residents take during their T32 year. Our current training protocol involves weekly research meetings and a monthly check-in with collaborators, quarterly journal club, and opportunities for OR and clinic shadowing.

My research interests center around the use of institutional data from our academic center as well as a unique curated head and neck cancer data set developed from the VA Informatics and Computing Infrastructure within the Veterans Administration. We have thus far looked at cardiovascular and neurovascular health but would welcome a motivated student to expand this dataset further to look at nutrition, mental health, and barriers to care.

Additionally, we have a basic science collaboration utilizing precision cut tumor slices from head and neck cancer specimens to probe mechanisms of activity and resistance to treatment within the tumor microenvironment.

The Carey lab is a basic science and translational laboratory in the Department of Otorhinolaryngology at the University of Pennsylvania School of Medicine in Philadelphia. We study head and neck cancer with the goal of improving our ability to diagnose and treat this challenging disease. Our research is at the interface between cancer neuroscience, cell biology, immunology, microbiology, pharmacology, and genetics. We are specifically interested in understanding how head and neck cancer cells interact with their local environment through G-protein coupled receptors including taste receptors and how the involved signaling pathways can regulate important cellular processes. Our hope is that we can leverage taste receptors as biomarkers or therapeutic targets for treating head and neck cancer. We work closely with Dr. Robert Lee, a world-renowned physiologist within our Department, combining his lab’s expertise in airway physiology to study malignancy. 

Fellowship students will be involved in lab-based projects studying head and neck cancer pathophysiology. Basic science techniques will include head and neck cancer cell culture, live cell imaging, growth and metabolism assays, and gene expression analysis. Prior basic science experience in biochemistry and molecular biology is preferred but not required. Students will also have the opportunity to interact with head and neck surgery faculty in the operating room and clinic throughout the year and assist with tissue procurement from these clinical sites.  Students will be involved with research projects that are conducive to obtaining peer-reviewed publications and presentations at national and international meetings.

Dr. Kevin Chandler, leader of the Laboratory for Functional Glycoproteomics within the Florida International University College of Medicine, is eagerly seeking research fellows to pursue basic research in head and neck cancer glycoimmunology with the goal of identifying new therapeutic targets.

Immune checkpoint inhibitors demonstrate incredible promise for the treatment of recurrent/metastatic head & neck squamous cell carcinoma (HNSCC), leading to higher progression-free & overall survival. By targeting inhibitory PD-1/PD-L1 interactions, PD-1 inhibitors such as pembrolizumab stimulate T-cells, enabling the immune system to respond to & destroy cancer cells. However, intrinsic & acquired resistance to checkpoint inhibitors presents a major barrier to the success of these therapeutics.

A potential mechanism of anti-PD1 resistance arises from the startling ability of some tumor cells to produce immunoglobulins (usually produced only by B cells). Tumor-derived immunoglobulins (tIgs), aberrantly modified with sialic acid sugars, inhibit T cell proliferation, & reduce effector T cells, via direct interaction with sialic-acid binding immunoglobulin-type lectins (Siglecs) expressed on T cells. Siglec receptors and their sialic acid-bearing ligands represent a less-targeted family of immune inhibitory receptors. tIgs have been described in cervical, ovarian, & esophageal cancers, with immunosuppressive roles. However, their role in HNSCC treatment resistance has not been defined. There is a critical need to study the role of tIgs in HNSCC anti-PD-1 treatment resistance.

We hypothesize that aberrantly sialylated tIgA1 contributes to immunosuppression & anti-PD-1 treatment resistance in HNSCC, via the Siglec pathway. Specifically, we propose that immuno-inhibitory interactions between tumor-associated immunoglobulin A1 (tIgA1) expressed by HNSCC cells and Siglec receptors on T cells, inhibit proliferation and infiltration of cytotoxic T-cells into tumors, an unexplored mechanism of resistance to anti-PD-1 therapy in HNSCC.

To elucidate the role of tIgA1 in anti-PD-1 resistance, the following aims are proposed for a research fellow to pursue: (1) Identify Tumor-Derived IgA1 Glycosylation Sites with Aberrant Sialic Acid Modifications & Characterize tIgA1 Interactions with T cells, (2) Define the Effects of Sialylated tIgA1 on T Cell Proliferation & Effector T cell Function, and (3) Assess the Role of Sialylated tIgA1 in anti-PD-1 Resistance. By demonstrating the contribution of aberrantly sialylated tIgA1 to immunosuppression & anti-PD-1 treatment resistance in HNSCC, the proposed research has strong potential to uncover a new therapeutic target and expand the reach of immunotherapy in HNSCC. Successful completion of these studies will provide the necessary data to support studies, larger in scope, designed to develop therapeutic strategies circumventing aberrantly sialylated tIgA1 in anti-PD-1 resistance in HNSCC.

Our laboratories have several areas of interest described below and our integrated translational and clinical scientist team is focused on the design and execution of clinical trials and the associated correlative science. We have an established, dedicated program for students that focuses on education in the conduct of research which includes training in statistics, medical writing, presentation and ethical conduct of research. We also have a formalized mentorship track which provides a basic scientist mentor and clinician scientist for each student. The trainee would have flexibility in the choice of project but for example we do have a recently funded and opened investigator initiated clinical trial focusing on basal cell carcinoma of the head and neck which we anticipate will run for the next two years and may be ideal. This mentorship program be aimed at supporting a student to develop the fundamentals of a clinician scientist career throughout a year long long opportunity in the one of the following areas of research:
Head and neck squamous cell carcinoma tumor microenvironment / tumor metabolism
Exosomes and small extracellular vesicles
Cancer genomics
Immunotherapy Clinical Trials

My research laboratory utilizes tissue and blood-based approaches for studying HPV genomics with a focus on development of liquid biopsies for detecting, diagnosing, and tracking HPV-associated cancers. We have developed multiple custom approaches for detecting cell free HPV DNA and have demonstrated that these approaches can be applied as highly accurate diagnostic tests and methods for tracking treatment response . We have also demonstrated that cell free HPV DNA is detectable more than three years prior to cancer diagnosis and thus could be a potential screening tool. One of these assays is now undergoing clinical rollout as a CLIA/CAP lab at Mass General Hospital and will be available for clinical care in 2023. This work is supported by both R03 and R21 NIH grants. In tissue we leverage next generation sequencing and computational approaches to elucidate how mutations occur in both the HPV genome and HPV-associated cancers, in particular from APOBEC mutagenesis, and how these alterations impact tumor behavior. Our laboratory also studies tissue and blood based biomarker approaches for non-HPV-associated cancers, with a focus on immunotherapy. This work is funded from grants from NIH (K23), Harvard Catalyst (KL2), foundations (AHNS, ACS, NASBS) and industry (Calico, BMS, Predicine). Lastly, I am actively involved in clinical trials as both a PI and through translational correlative studies with support from industry partners. My laboratory currently takes 2-3 medical students per year for one year immersion experiences in which students work with me to select a translational project to lead which serves as a basis for learning and growth. More recently, our focus has been to take medical students from populations underrepresented in science. Thus, our scientific focus and mission fits will with the Eddie Méndez Fellowship Award.

The Head and Neck Signaling Lab at UCSF is co-directed by Dr. Jennifer Grandis, Dr. Patrick Ha, and Dr. Daniel Johnson. Our lab is focused on studying the molecular signaling pathways involved in carcinogenesis in head and neck squamous cell carcinoma and adenoid cystic carcinoma. Depending on the experience and interest of the applicant, we can help train and create projects that can be accomplished within the 1-year rotation.

Transdisciplinary, population aspects of head and neck cancer, from prevention to early detection to survivorship, to quality of life, psychosocial outcomes and cancer-related disparities. Please see the attached Biosktech for context.

Introduction:
As a dedicated and passionate researcher, I have developed a strong interest in quality improvement projects, particularly in the area of Enhanced Recovery After Surgery (ERAS). Additionally, I am enthusiastic about conducting large-scale database studies. In pursuit of my research goals, I have been involved in leading successful projects and mentoring research fellows. With a proven track record of achieving high publication rates, I am excited to embark on new research projects ideally suited for medical students that can be completed within a one-year fellowship.

Research Interest 1: Enhanced Recovery After Surgery (ERAS)
Enhanced Recovery After Surgery (ERAS) is an evidence-based, multidisciplinary approach that aims to optimize patient outcomes and speed up recovery following surgery. My research interests in ERAS encompass various aspects, including identifying best practices, evaluating the impact of specific interventions, and developing standardized protocols for specific surgical procedures.

Within a one-year fellowship, I plan to conduct a comprehensive study on the implementation and outcomes of ERAS protocols in a specific surgical population. This project would involve designing a prospective cohort study, collecting and analyzing relevant data, and assessing the impact of ERAS on patient outcomes, such as length of hospital stay, postoperative complications, and readmission rates. Additionally, I would explore the barriers to ERAS implementation and identify strategies for successful integration into routine clinical practice.

Research Interest 2: Large-Scale Database Studies
Large-scale database studies provide an invaluable opportunity to investigate patterns, trends, and associations within vast amounts of patient data. Recognizing the power of data-driven research, I am keen to leverage existing healthcare databases to generate evidence that can inform clinical decision-making and improve patient care on a broader scale. My interests in this area extend to analyzing population-level outcomes, evaluating healthcare interventions, and identifying potential risk factors or prognostic markers.

For a one-year fellowship, I propose conducting a retrospective analysis using a large healthcare database, focusing on a specific disease or condition of significant public health importance. By exploring this rich dataset, I aim to identify trends, disparities, and factors influencing disease progression or treatment outcomes.

Track Record and Mentoring:
Over the past three years, I have successfully supervised research fellows, each of whom achieved a minimum of 10 publications within a year. I am committed to providing a supportive and intellectually stimulating environment for aspiring researchers. In collaboration with a medical student during the one-year fellowship,

Retrospective head and neck oncology projects. Robotic head and neck surgery.

I would be delighted to mentor a student in basic/translational and/or clinical research. Our lab studies immune effects of novel combination therapies for head and neck cancer. Techniques include in vitro cell line work, mouse models, and study of human tumor and blood samples from patients with cancer. We are also interested in salivary tumor biology.

Many of our clinical research projects are in geriatric oncology, looking at how older patients function- and survive- after treatment. This is an increasingly important topic as our population ages, and the percent of patients with cancer who are over age 65 is increasing exponentially. We have well-established clinical RedCAP databases that can be used for this purpose, and we also have access to excellent statisticians at our Cancer Institute. The clinical volume at our institution is among the highest in the Southeast United States, so we have large numbers of cases in these databases.

I am a head and neck microvascular reconstructive surgeon with an interest in global health and local disparity research. My current ongoing work includes assessing head and neck cancer outcomes at Muhimbili National Hospital in Tanzania. I am involved in ongoing collaborations looking to improve quality of tracheostomy care and addressing malnutrition of head and neck cancer patients at Muhimbili National Hospital. In additional to this work, I work clinically at both UCSF's cancer center and the Zuckerberg San Francisco General (ZSFG) Hospital, the latter of which services immigrant, homeless, and minority populations in San Francisco. Finally, I have been involved with the Global OHNS Initiative, a network of clinicians and researchers globally interested in global health in otolaryngology.

Potential year long project for medical students working with me include
1) assessing clinical outcomes of head and neck cancer patients at ZSFG and comparing those to the outcomes of UCSF
2) involvement in a portion of ongoing global health projects in Tanzania (survey development and assessment, qualitative research)
3) developing a project in collaboration with Global OHNS Initiative members/ collaborators