Thomas Research 200Carissa Thomas, M.D., Ph.D.

Assistant Professor

 

 

University of Alabama Oral Microbiome Biobank

We have established a microbiome biobank at UAB from patients with oral cavity and oropharyngeal squamous cell carcinoma (SCC). Biospecimen collection includes oral swab and brush specimens, saliva, stool, peripheral blood, and tumor tissue. In addition, we are collecting clinicopathologic data, oral care habits, diet history, and antibiotic use on these patients. This biobank will be utilized for collaborative projects that can provide prognostic information, guide treatment selection, and ultimately improve survival in oral cavity and oropharyngeal SCC. 

Understanding Interactions between the Microbiome and Oral Squamous Cell Carcinoma and the Tumor Microenvironment

Each year 3% of all new cancer cases are oral cavity cancer, which equates to approximately 53,000 cases per year. Rates of survival have remained poor at approximately 60% and relatively stagnant for decades. The Thomas lab is focused on understanding how bacteria in the oral cavity (microbiome) may regulate chronic inflammation and malignant transformation in head and neck cancer as well as metastatic disease. We are investigating the oral cavity microbiome as a biomarker of disease and predictor of prognosis with the future goal of altering the microbiome to improve treatment response and prevent recurrence and metastases. Active areas of scientific work include: 1) bacterial regulation of PD-L1 expression on tumor cells and immune cells in the tumor microenvironment; 2) bacterial regulation of immune cell populations in the tumor microenvironment, specifically macrophage recruitment and differentiation into tumor associated macrophages; 3) bacterial regulation of tumor cell invasiveness. 

Characterization of the Microbiome and its Role in Head and Neck Cancer-Related Pain

Oral squamous cell carcinoma (OSCC) is associated with moderate to severe pain at the primary site affecting speech, mastication, and swallowing. In addition, patients with OSCC typically require higher doses of opioids and are at increased risk for opioid dependence resulting in a reduced quality of life and survival. Effective pain management in patients with OSCC is challenging because of our limited understanding of mechanisms of cancer pain. In other disease processes, the gut microbiome is known to modulate pain via mechanisms of bacteria-derived mediators, metabolites and neurotransmitters acting on immune cells and nociceptors (pain receptors). Our research aims to identify biomarkers within the local oral cavity microbiome and distant gut microbiome that modulate OSCC cancer pain. Understanding mechanisms and mediators of pain in OSCC will allow for development of alternative targeted therapies and potentially reduced opioid dependence.

Modifying the Saliva Microbiome to Reduce Post-Operative Wound Complications in Patients with Head and Neck Cancer

Many head and neck cancers are treated with surgery, which involves tumor extirpation and reconstruction with local, regional, and microvascular free tissue transfer reconstructions. Wound complications are frequent due to a multitude of factors including smoking, diabetes, prior radiation or chemoradiation, immunosuppression, malnutrition, hypothyroidism, and constant contact with saliva. Wound complications are a burden to our healthcare system by increasing hospital length of stay and requiring additional surgeries. In addition, poor wound healing increases patient morbidity, delays the ability to receive additional cancer treatment such as radiation, and delays the ability to resume eating by mouth and speaking. These delays impact survival as well as quality of life. Our research is examining if modifying the saliva microbiome and decreasing bacterial load can reduce post-operative wound complications in patients with head and neck cancer.

Outcomes Following Microvascular Reconstruction of Head and Neck Cancer Defects

An essential component of excellence in patient care is frequent assessment of outcomes and identification of ways to reduce complications and improve outcomes for our patients. A wide variety of patient outcomes such as medical and surgical complications, wound complications, speech, swallow, oral competence, cosmesis, quality of life, and decision regret are being assessed in patients undergoing microvascular reconstruction as part of their treatment for head and neck cancer. These outcomes are being measured in an institutional as well as multi-institutional fashion in order to improve the form and function of free tissue transfer.

Targeted Fluorescence Imaging to Predict Flap Failure During Reconstructive Surgery

Regional and microvascular free tissue transfer reconstructions are the standard of care in treating patients with head and neck cancer. These reconstructive methods (i.e. flaps) are reliable but when complications with viability do occur, they can have significant morbidity. In collaboration with Dr. Jason Warram, we aim to use imaging agents targeted to key receptors of angiogenesis and vessel repair to guide clinical assessment of viable tissue during reconstructive surgery. By utilizing fluorescence imaging, viability information can be provided as early as post-operative day 0 to assess areas of neovascularization and anastomosis. The timely nature of this information can guide the reconstructive surgeons to areas of flap compromise and failure, allowing for earlier interventions and thereby improving patient outcomes.


Thomas Research 200Jason Warram, Ph.D.

Associate Professor

 

 

Fluorescence Screening and Diagnosis of Oral Cancer

In collaboration with Dr. William Carroll (Otolaryngology) and Dr. Anthony Morlandt (Oral maxillofacial surgery), we are developing a diagnostic, plasmid-based system to screen for oral cancers in the clinical or home-based setting. By coating a plasmid in cationic polymers for transfection, the system can be applied to the oral cavity as a rinse. Once transfection occurs, the upregulation of a cancer promotor will lead to the production of a fluorescent protein for localized imaging of cancer. Since the imaging reporter is driven by the relative cancer gene expression, the fluorescence can be used to localize suspicious lesions, and additionally provide initial diagnostic information. This study is pending funding from the American Cancer Society.

Quantifying Imaging-transcriptomic Signatures of Therapeutic Response in Head and Neck Cancer

In collaboration with Dr. Anna Sorace (Radiology), the overall goal of this project is to identify and exploit quantitative imaging-transcriptomics signatures of treatment response to combination targeted and cytotoxic therapies in head and neck cancer tumors. We aim to harness changes in tumor transcriptomic and spatial heterogeneity extracted from advanced molecular and functional imaging (MRI & PET) to develop effective, personalized, and targeted therapy regimens for head and cancer. This study is pending funding from the NIH.

Comparison of 89Zr panitumumab and 18F-Fluorodeoxyglucose to Identify Head and Neck Cancer

In collaboration with Dr. Suzy Lapi (Radiology), this study is a pending clinical trial to determine the sensitivity and specificity of PET imaging with 89Zr panitumumab in the identification of primary head and neck cancer. Tumor SUV and TBR generated from 89Zr panitumumab and 18F-Fluorodeoxyglucose will be compared to pathological and surgical information to determine the optimal agent for identifying unknown primary disease and tumor extent. This study is pending IRB approval.

Targeted PET Imaging to Predict Response to Immunotherapeutic Treatment of Head and Neck Cancer

Early prediction of immunotherapeutic response is critical to guide oncologists using this unique cancer treatment. Pseudo-progression of tumors enduring this treatment further complicate the ability to predict responders, and conventional imaging modalities have not proved adequate. In collaboration with Dr. Ben Larimer (Radiology), we propose to utilize a novel PET imaging probe to target downstream effectors of tumoral cytotoxic T cells that are key to successful immunotherapeutic treatment. Preliminary studies are ongoing using human tissues and syngeneic mouse models to eventually translate these imaging strategies to human patients undergoing head and neck cancer treatment.

Reduction of Tumor-Positive Margins in Oncology Surgery

In collaboration with Dr. William Carroll (Otolaryngology) and Dr. Hari Jeyarajan (Otolaryngology), this ongoing Phase II clinical trial (ClinicalTrials.gov Identifier: NCT04511078) seeks to identify the clinical benefit of using fluorescence guided surgery during trans oral robotic surgery. Utilizing an investigational new imaging agent, panitumumab-IRDye800, head and neck tumors are illuminated during surgery, expanding the visual information used to guide the excision. The use of this technology during robotic surgery has the potential to reduce the rates of positive margins and improve patient outcomes. This study supported by the NIH.

Fluorescence-guided Surgical Excision of Cholesteatoma Using Targeted Peptides

The treatment of large or complicated ear cholesteatomas require surgical excision to prevent loss of hearing or bone erosion. Complete removal of all cholesteatoma tissue is essential to avert recurrence and avoid further complications associated with this disease. In collaboration with Dr. Ben Larimer (Radiology), cholesteatoma tissues from human patients are being screened using a unique drug discovery platform combining phase display with small biological peptides to develop cholesteatoma-specific imaging agents. These targeted agents can be used by the surgeon to illuminate and localize cholesteatomas leading to more complete excisions and improved patient outcomes.

Targeted Fluorescence Imaging to Predict Flap Failure During Reconstructive Surgery

In collaboration with Dr. Carissa Thomas (Otolaryngology), we aim to use imaging agents targeted to key receptors of vessel formation and repair to guide clinical assessment of viable tissue during reconstructive surgery. By utilizing fluorescence imaging, viability information can be provided as early as the day of reconstruction to assess healthy areas of neovascularization and anastomosis. The timely nature of this information can inform and guide the reconstructive surgeons to areas of failure thereby improving the surgical success and patient outcomes. These studies are ongoing with multiple reports pending publication.

Multi-parametric PET Imaging of Vestibular Schwannoma

The majority of vestibular schwannoma (VS) tumors display significant slow growth or may even decrease in size after diagnosis and may be monitored annually without requiring treatment. Surgical resection with preservation of the facial nerve or stereotactic radiosurgery are the primary treatments for VS, although both are associated with patient co-morbidities that correlate with tumor size. Therefore, it is desirable to treat growing VS while the tumors are small. In collaboration with Dr. Erika Walsh (Otolaryngology) and Dr. Suzy Lapi (Radiology), the long-term goal of this project is to identify non-invasive imaging strategies that will aid the prognostic assessment of VS in human patients. By targeting elements of growth and proliferation, PET imaging agents can distinguish between fast and slow growing VS tumors in human patients. We propose that multi-parametric PET imaging will overcome the limitations of [18F]FDG PET alone and will provide clinically meaningful metrics to distinguish proliferative rates in VS tumors. This study is pending funding from the NIH.