Resident Research

Goals

Otolaryngologists, as specialists, are compelled to be efficient researchers in order to provide superior care to their patients.  On a daily basis we encounter complex clinical scenarios that require us to formulate diagnostic differentials (i.e., hypotheses), plans of investigation (i.e., study design), acquire and integrate clinical information from a variety of sources (i.e., data analysis) in order to formulate diagnoses and treatment plans.  Characteristically, we rely on the available body of knowledge, be it our own, our colleagues' personal experiences, case reports, prospective studies, etc.  Inherent to utilizing this information is the ability to objectively understand and evaluate the applicability and reliability of this body of knowledge to the relevant scenario.

With this in mind, the goal of the research rotation is not to create physician-scientists who will devote a substantial portion of their careers to "bench-top" research.  Although the six-month duration of this rotation may not be sufficient for that purpose, it may stimulate the resident into pursuing additional research training through a fellowship.  The fundamental goal of the research rotation is to empower the resident with skills that will facilitate a clinician specialist's day-to-day activities.  These skills include the appreciation of how research studies are designed, the ability to evaluate and critically analyze research findings and effective utilization of resources (e.g., on-line databases, institutional support services, etc.).

The ideal research project for a research rotation is one that the resident can be involved in from inception to publication. It is, of course, understandable that a beginning-to-end involvement is not always feasible.  In the past, some projects have required the participation of multiple residents to reach their final goal.

Overview

1.      Residents will participate in research activities for two 3-month periods.  One block will occur in the PGY3 and one in the PGY4.

2.      Residents will prepare for their research period in advance of the actual rotation (preferably during PGY2), in order to be able to start the project without delay.  Residents will update the Director of Research on their progress toward project selection.  After residents have met with and received approval from a Faculty Sponsor, he/she must write a proposal to submit to the Director of Research prior to initiating their research.  Director of Research will review and evaluate the proposal for educational and scientific value. 

a.  Approval of the proposal is necessary to initiate the project. 

b.  Approval must be received, at least, one month prior to resident rotation.

c.  Approval qualifies the proposed project for funding from the Division.

3.      Beside the expected written research proposal prior to the start of the rotation, A project progress report is required at the end of the rotation.  Residents will present their proposals and findings in didactic conferences.  It is hoped that  a progress report can serve as a first draft of a report to be submitted for publication.

4.      Research projects will have faculty advisors and oversight of the projects will be by the appropriate faculty advisor.  The Director of Research will monitor resident progress and provide further guidance, as needed.

5.      The Division, within reason, provides funding for resident research projects.  The research proposals prepared by the residents are expected to be of sufficient quality to allow submission to funding agencies.  When a project is deemed to be beyond the resources available to the residency program every effort should be made to submit the proposals for outside funding when available and appropriate. 

Resident Research - Spotlight

Fig. 1. PGA/PLLA implant.

Fig. 2. Diagram of the experimental apparatus used to measure collapsing pressures. Adapted from McFawn and Mitchell HW.

Fig. 3.  Ex vivo endoscopic subglottic views showing changes of a 4 mm PGA/PLLA specimen when subjected to increasing negative pressures, pictured from left to right, top to bottom: 0 cm H₂O, -10 cm H₂O, -30 cm H₂O, -50 cm H₂O.

Fig. 4. Area slope comparisons between cartilage and PGA/PLLA specimens when subjected to closed system pressures (area measured in pixels).

Fig. 5. Ex vivo endoscopic subglottic views showing changes of a 4 mm PGA/PLLA specimen when subjected to increasing negative pressures, pictured from left to right, top to bottom: 0 cm H₂O, -10 cm H₂O, -30 cm H₂O, -50 cm H₂O.

Fig. 6. Histologic slides prepared from axial cuts through the normal and postsurgical cricoid cartilages, pictured from left to right, top to bottom: 1) low-power hematoxylin-eosin (H&E) stain of a normal specimen, 2) low-power H&E stain of cartilage implanted specimen, 3) low-power H&E stain of 4 mm PGA/PLLA implanted specimen (resorbed), 4) magnified H&E stained view of 4 mm PGA/PLLA specimen showing remucosilized lumen (×20 magnification), 5) trichrome stain showing an intact epithelium and fibrous tissue replacement of the PGA/PLLA implant (×10 magnification).

Research Opportunities

•Geriatric Otolaryngology

George Kuchel, M.D.; Associate Professor of Medicine, UCONN Center on Aging

•Head & Neck Oncology

Liisa Kuhn, PhD.; Assistant Professor, Department of Oral Rehabilitation, Biomaterials and Skeletal Development

Drug delivery systems provide a way to increase drug effectiveness and decrease systemic toxicity. The Kuhn lab is focussed on using biomaterials, such as nanocrystals of hydroxyapatite, (similar to what bones and teeth are made of) combined with polymers to formulate novel drug delivery systems for chemotherapy. Research projects in the Kuhn lab typically involve three components: preparation of the drug delivery system, drug release testing, and finally, proof of principle in vivo mouse studies. Three different recent mouse studies have shown that our calcium phosphate/cisplatin drug delivery system is more effective than systemic cisplatin at reducing tumor growth, and reduces systemic cisplatin toxicity. The rotation project would involve determining and gathering any additional animal data required to clinically implement this less toxic means of delivering chemotherapy to head and neck cancer patients.
 

Jeffrey Spiro, MD.;  Professor, Department of Surgery

Henry M. Smilowitz, Ph.D.; Associate Professor, Department of Pharmacology

A number of research projects in the fields of head & neck cancer, cancer immunotherapy, cancer therapy, tumor and vascular imaging.  Please, click here for more information.

•Pediatric Otolaryngology

Scott Schoem, M.D.; Associate Professor, Connecticut Children's Medical Center

Several retrospective studies are available for the resident to initiate.  In addition, a project on safety and duration of providing anesthesia through the LMA in an animal model is at its inception and open to resident contribution.

•Plastic/Reconstructive Surgery

Rajiv Chandawarkar, M.D.; Associate Professor, Department of Surgery

Opportunities available in plastic surgery/reconstructive surgery, as well as, immune modulation using heat shock protein gp96.  Please, contact Dr. Chandawarkar for additional detail.

•Otology/Neuro-otology

Duck O. Kim, D.Sc.; Professor, Department of Neuroscience

 Hypothesis 1:  The adulthood auditory adaptive plasticity is enhanced in a barn owl engaging in active live-prey hunting by the enriched auditory/visual/motor experience compared to that in an owl which is passively fed with dead-mouse food.

 Hypothesis 2:    Adulthood plasticity of the auditory space map in the midbrain requires descending instructive signals from the forebrain gaze field called the "auditory archistriatum" (AAr).

             In the behavioral part of the study, each owl will be trained to turn its head toward a sound or light source. The owl’s head-orienting behavior will be measured using a magnetic search-coil system. In the physiological part of the study, we will place a microelectrode in the owl's brain under anesthesia and record responses of neurons of the auditory space map in the midbrain optic tectum (the bird homolog of the mammalian superior colliculus) and determine the relationships between the auditory and visual receptive fields of the neurons.  

            Each adult owl will undergo a period of wearing prismatic spectacles that shift the visual field by 17 degrees. Hypothesis 1 will be tested by comparing the results from owls that engaged in active live-prey hunting with those from owls that were passively fed. Hypothesis 2 will be tested by comparing the results from intact owls (that engaged in active hunting) with those from owls whose auditory forebrain gaze field AAr were electrolytically lesioned at an adult age on both sides of the brain prior to the period of prism wearing.  

            The present study is significant because a proof of the existence of a descending instructive signal from the forebrain to the midbrain that is essential for manifestation of adulthood auditory adaptive plasticity will open up many new important questions to follow up. For example, what are the relative roles of the forebrain and midbrain in the overall auditory-localization and gaze-shift behaviors under the normal condition and under the condition of a sensory discordance (e.g., with prism wearing)? What is the nature of the forebrain instructive signal transmitted to the midbrain? What are the cellular mechanisms whereby the forebrain instructive signal produces the midbrain adaptive plasticity? 

Douglas Oliver, Ph.D.; Professor, Department of Neuroscience

Themes

#1 – Studies of functional zones in the auditory midbrain (inferior colliculus). All neurons in the auditory midbrain are not alike since they seem to prefer different types of sound stimuli. For example, neurons have different types of responses to sounds located in space. Our general hypothesis is that neurons are grouped in small functional zones and receive inputs from only a restricted number of sources. These inputs will determine the type of response. The experiments for this project will use recordings of the responses of neurons in the inferior colliculus to acoustic stimuli to tell us what type of auditory information they process. Morphological markers introduced through the recording electrodes will tell us about the inputs to these neurons. This project will teach you about small animal surgery, auditory electrophysiology, and histology including immunocytochemistry. For a research rotation, you will test a single, narrowly defined hypothesis about the inputs for one type of response.

 #2 – Neuron involved in sound processing in the auditory midbrain. Auditory processing also depends upon the specific types of neurons involved in the networks and the types of synapses on them. Previously, we have identified neurons in the inferior colliculus by their morphology, neurotransmitter content,  axonal targeting, and most recently by their different firing patterns. The firing patterns can be explained by the expression of different types of potassium currents. Our current experiments use the brain slice to study the relationship of these factors in neurons with different functional properties. For a research rotation, you will test a single hypothesis concerning one set of relationships: for example, neurons with sustained-regular discharge patterns are GABAergic projection neurons. 

#3 – Activity-dependent plasticity in the auditory system. Abnormal sound environments that cause increased or decreased levels of neural activity may alter the physiology of the central auditory system and impact hearing. We are beginning the investigation of central changes in response to augmented acoustic environments (non-damaging sounds) or noise trauma. An example of an augmented acoustic environment is the exposure of rat pups ages P9-P30 to a single, 60 dB pure tone for 18 hr/day. This sound exposure during development results in an increase in the numbers of neurons tuned to that frequency and a distortion of the tonotopic map in the auditory cortex of the adult.  We are currently in the process of showing that a similar change occurs in the inferior colliculus of the midbrain. After noise trauma with narrow band sound, partial deafness occurs due to cochlear damage. Studies have shown that in the auditory cortex, neurons change in the cortex that are tuned to the cut-off frequency at the normal, low-frequency edge of the hearing loss. Neurons tuned to the cut-off frequency also increase in number. We are participating in studies to see if this response also occurs in the midbrain. Research rotations would investigate a small part of these problems. We plan electrophysiological experiments to test hypotheses that synapses are changed in response to altered activity levels, and we plan anatomical experiments to test hypotheses that axonal development is altered in the young animals exposed to an augmented acoustic environment. 

#4 – Novel questions. Students who wish to formulate their own novel questions about the synaptic organization of the auditory system are more than welcome.

Steven J. Potashner, Ph.D.; Professor, Department of Neuroscience

Synaptic and transmitter biochemistry and plasticity in the in the auditory parts of the adult brain.   Click here for more information.

•Rhinology

Marion E. Frank, Ph.D.; Professor, Oral Diagnosis

Our research focus in on the chemical senses (taste, smell and oral nociception (pain)) included within the neurosciences. Chemosensory research has come into its own during the last 15 years, due to the identification of molecular receptors for taste, smell and nociceptive stimuli and an increased understanding of coding of chemosensory information by the nervous system. The group of investigators: Marion Frank, Tom Hettinger, Brad Formaker, Larry Savoy, has a lengthy experience of association of basic and clinical research, which offers a fertile environment for innovation and application.

            Our funded research, on humans and hamsters (Mesocricetus auratus), is focused on taste quality coding: the mechanisms by which the nervous system codes for the qualities of taste [sweet, salty, bitter, etc.]. Projects address (1) the human salty and bitter taste qualities, which are studied by applying chlorhexidine and weak electric currents to the tongue, treatments that interfere with the tasting of salts; and (2) taste quality coding of stimuli in the sweet and bitter domains by golden hamsters (Mesocricetus auratus), neurophysiolgically and behaviorally. The relationship between the neural responses and the animals’ abilities to discriminate stimuli is used to define taste coding strategies used by the central nervous system.

 Project #1. Hamsters are repelled by cycloheximide, a protein synthesis inhibitor, at concentrations of less than 1 mM. Its aversive potency increases dramatically after a single exposure. Yet it is not known whether cycloheximide is a taste stimulus for hamsters. Humans can hardly detect the compound by taste. A possible project would require electrophysiological recording from the chorda tympani nerve in 2 groups of hamsters, those that had been exposed to cycloheximide and those that had not been exposed to cycloheximide. This experiment would address a possible “induction” of taste receptors for dangerous compounds like cycloheximide. The project would involve learning micro-neurosurgical techniques to isolate the hamster chorda tympani nerve, electrophysiological techniques to obtain recordings, techniques of computerized analysis to quantify the data, and statistical analysis to evaluate the significance of the data. Approval of the Animal Care Committee for the use of hamsters, which will be euthanized after experiments, must be obtained for the project.

 Project #2. Weak cathodal electric currents inhibit the human salty and bitter tastes of chloride salts. One hypothesis regarding the mechanism of this inhibition is that the perceptions of tastes elicited by cations are reduced because the currents draw stimulatory ions away from the taste receptors. Another hypothesis is that the inhibition results from the current presenting inhibitory chloride anions to the receptors. A possible project would involve applying weak electric currents (-20 mA, -40mA) through various ionic solutions (e.g., NaCl, MgSO₄) while presenting them to the human tongue to taste. Measures of (1) taste intensity on a visual analog scale and (2) identification of taste quality from a closed list of names would be obtained. This project provides training in testing hypotheses about the mechanisms that activate a human sensory system by using the human response as the dependent variable. It requires learning psychophysical techniques, and methods of data analysis and the statistical evaluation of results. IRB approval of the use of human subjects will have to be obtained for the project.

 Project #3. In the course of ENT surgery in the human middle ear, the chorda tympani nerve may be damaged. Little is known about consequences of this damage on the ability to taste, initially, or whether there is any recovery of gustatory function. A possible project would involve testing a patient before and after middle-ear surgery. Measurements would include whole mouth and spatial tests of taste and electrogustometry; tests used by the UConn Taste and Smell Clinic. Other information on patients would include notes from surgeons re. status of the chorda tympani nerve, pre and post-surgery, and photographs of the tongue pre and post surgery to identify changes in the structure of fungiform papillae on the operated side. This project provides training in testing clinical hypotheses about a sensory system, measuring human sensation, and relating function to surgical/structural variables. It requires learning methods of testing sensory function in a clinical setting, as well as data analysis and statistical evaluation of results. IRB approval of the use of patient subjects will have to be obtained for the project.

•General Otolaryngology

Kourosh Parham, M.D., Ph.D.; Assistant Professor, Department of Surgery

Available to pursue prospective studies of patient tolerance of transnasal esophagoscopy (TNE) and its clinical utility.  TNE is a novel clinical tool useful to perform screening examinations of the esophagus in patients with laryngopharyngeal reflux, gastroespohageal reflux, dysphagia, globus sensation, head and neck cancers, etc.  The study is in its infancy and is being developed by one of our residents and would welcome additional resident contributions.