Our Research Pursuits
Our department consists of several teams which focus both on basic and clinical and translational research. The department has a large laboratory in the Research Biopark, which is located across the street from the University of Maryland School of Medicine and a walking distance from our clinical offices and the operating rooms. There are multiple clinical and basic science PIs in the lab; their teams focus largely on genetic hearing loss and tumor immunology with an eye towards translational applications. The various teams work within a shared open space and hold joint lab meetings and journal clubs to promote collaborative endeavors. Additionally, the Department has established strong alliances with basic science departments, such as Biochemistry and Immunology, to create a multi-disciplinary network that enhances translation research pursuits.
The team of Dr. Ahmed is focused on understanding how the retinal and inner ear sensory epithelia develop and function. Dr. Ahmed’s research interests consist of: (1) Inherited human disorders of retina and inner ear, like Usher syndrome (USH); and (2) Oculocutaneous Albinism (OCA). The studies under investigation are designed to answer the following broad questions: What are the precise mechanisms of various forms of hearing and vision dysfunction? What are the genetic factors that determine light sensitivity? How do the pathogenic mutations in disease-causing genes affect the ear, eye and skin structure and function? And which molecules or genetic factors can exacerbate and/or mitigate the effects of disease-causing genes? For these studies, families segregating inherited USH and OCA are being collected. Mutant mouse and zebrafish models have been developed and we evaluate them to understand the function of new proteins. Functional analysis of the newly identified genes associated with deaf-blindness and OCA promises new insights into the molecular mechanisms of vision and auditory development and functions and will facilitate the rational design of potential therapies.
Dr. Eisenman’s research interest are focused on pulse-synchronous tinnitus. He studies the pathophysiology, radiologic characteristics and the development of new treatments for pulse synchronous tinnitus that results from sigmoid sinus diverticula. Dr. Eisenman’s research is primarily clinical in nature.
Dr. Hertzano’s research team (the Laboratory of Inner Ear Developmental Genetics) uses cell type-specific approaches to (1) define the key regulatory events that lead to cell type-specific differentiation. Specifically, identification and characterization of transcriptional cascades that lead to hair cell terminal differentiation and survival as a crucial step in developing regenerative treatments for hearing loss; and (2) defining the molecular events as a result of acquired and noise-induced hearing loss to develop novel approaches for prevention and treatment of these problems. The team uses cell type-specific genomic approaches in mice and zebrafish, followed by validation using genetically engineered animal models and classic experimental and developmental biology techniques.
Dr. Riazuddin’s team is focused on understanding the molecular and genetic basis of hearing impairment. This is done by ascertaining large human families segregating hearing loss and through genetic screening; disease causing mutations are identified in these families. The identified mutations are further studied by analyzing the orthologous mutant mouse models, which are evaluated for developmental, structural and physiological defects of the inner ear. This will help us better understand the mutated genes and the underlying molecular mechanism of the hearing process. Identification of such genes will help in early and more accurate diagnosis for certain forms of hereditary hear impairments. The lab uses various approaches ranging from genetic analysis of human DNA samples to screen and identify the candidate genes, to molecular biological approaches to determine the expression of gene under study at protein /RNA level. To further study the target genes different model systems are exploited which include but are not limited to mouse, Zebrafish etc, where expression, localization and morphology of the inner ear is compared to wild type controls.
Dr. Schulze is currently working in collaboration with Dr. Strome in developing an approach that can be used in treatment of tumors using Chimeric Antigen Receptors (CARs). These receptors can be put into the patient’s own T cells to treat their tumors. We are developing novel CARs that can target tumors of the Head and Neck and also inhibit interactions with T cells that can inhibit or inactivate the T cell’s function. This BiCAR approach is not only novel but could be an important improvement in current treatment using this new technology. Another focus in the laboratory is to develop novel molecular constructs that can be used as sensitive biosensors for biological detection (biological weapons, virus and pathogen testing), medical testing and for the protection of food and agricultural products. The approach we have developed is to engineer a “universal biosensor” that can be used in combination with existing antibodies to rapidly develop novel tests for various applications.
Dr. Taylor is a surgeon-scientist whose clinical practice is dedicated to the comprehensive care of patients with cancer of the head and neck. He has established an academic-tertiary practice with patients referred for complex surgical management of SCCHN. His research goals are aligned with his clinical objectives: to improve the survival of patients with SCCHN. His lab has focused on factors impacting immuno-cytotoxicity and immune-tolerance. His lab has extensive experience working with SCCHN cell lines and murine xenograft tumor models. Based upon findings from his laboratory, he initiated and completed a multi-institutional clinical trial evaluating the impact of NK Fc?RIIIa polymorphisms on antibody-based therapy for SCCHN. This work has provided insight into which patients best benefit from antibody-based therapy for SCCHN. His lab currently has forged a collaboration with Dr. Zalzman’s lab and he has successfully established murine models to study head and neck cancer immortality mechanisms and behavior using xenografts Additionally, the two labs have combined to harvest adult mesenchymal stem cells to both improve their long-term survival in culture while preserving their differentiation potential ultimately facilitating advancements for regenerative medicine .
The Zalzman laboratory is focused on novel fundamental mechanisms controlling cellular immortality. The team studies cellular immortality and telomere repair in two major systems: adult stem cells and cancer cells. Unlike normal cells in our body, cancer cells don’t age. They activate mechanisms to bypass the aging process, gain immortality and continue to replicate indefinitely. Our goal is to characterize the components of a novel apparatus that allows cancer to bypass cell aging in order to ultimately allow the development of a new class of agents designed to target cancer immortality. Additionally, our lab has gained extensive experience in adult stem cell isolation and differentiation from multiple tissue sources. We develop novel protocols to enhance the replicative lifespan and the differentiation potential of adult stem cells. This research will allow the large scale expansion of adult stem cells required for future therapies of numerous diseases that are currently candidates for stem cell treatment.