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2-9-12 Research Project Titles – Otolaryngology Faculty
Amit Agrawal, MD
1. Food-Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer
Co-PI: Amit Agrawal, MD, (PI: Christopher Weghorst, PhD)
Project contribution 40%. Overall effort 5%.
Sponsor: NIH/NCI. R01 ($1,875,000)
Status: Active (12/1/07 - 8/30/12)
2. Principal Investigator, A phase 1b Pilot Study Evaluating Oral Administration of Freeze-Dried Black
Raspberries in Post-Surgical Appalachian Oral Cancer Patients (Investigator-initiated trial, Ohio State
University Comprehensive Cancer Center, funded by ACS grant “Chemoprevention of Oral Cancer in
Appalachia”).
3. Principal Investigator, Food-Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer
(Investigator-initiated trial, Ohio State University Comprehensive Cancer Center, funded by R01 NCI/NIH.
4. Principal Investigator, A Phase 3, Prospective, Open-Label, Multicenter Study of Lymphoseek-Identified
Sentinel Lymph Nodes (SLNs) Relative to the Pathological Status of Non-Sentinel Lymph Nodes in an
Elective Neck Dissection (END) in Cutaneous Head and Neck and Intraoral Squamous Cell Carcinoma
(Industry sponsored multi-institutional trial, OSU lead study site and lead authorship for
publications/presentations resulting from this trial). Initial results presented (oral presentation) at the Annual
Meeting of the Society of Nuclear Medicine, San Antonio, TX, June, 2011 (selected as top 10% abstract).
5. Principal Investigator, Evaluation of patients with squamous cell carcinoma metastatic to the neck with occult
primary tumors. Ongoing trial assessing clinicopathologic parameters as well as molecular correlates in
patients with HNSCC of unknown primary origin. (2 national presentations and 2 published manuscripts to
date). Molecular correlates ongoing.
6. Principal Investigator, Outcomes of Early vs Delayed Tracheoesophageal Voice Prosthesis Placement in
Patients Undergoing Primary Tracheoesopahgeal Puncture at the time of Total Laryngectomy. Have recruited
medical student Danny Jandali (MS III) to work on this project (Summer 2011). Will serve as his direct mentor.
Successful funding support by OSU Roessler Scholarship
7. Co-Principal Investigator, A Pilot Study Assessing Transoral Robotic Surgery (TORS) for Oral and
Laryngopharyngeal Benign and Malignant Lesions Using the DaVinci Robotic Surgical System. (PI: Enver
Ozer)
8. Investigator, Role of Tissue Autofluorescence in Patients Undergoing Surgery for Premalignant and Malignant
Oral Lesions (PI: John Kalmar). I am the lead investigator of the molecular correlates portion of this study
investigating correlation of molecular LOH markers with histopathologic and clinical autofluorescence
variables.
9. Investigator, Phase I trial of Vorinostat in the Treatment of Patients with Advanced Oropharyngeal Carcinoma.
(PI: Theodoros Teknos)
10. Investigator, Randomized Trial Comparing Vacuum-Assisted Dressing vs Traditional Bolster upon Healing of
the Radial Forearm Free Flap Donor Site (PI: Eugene Chio)
Eugene Chio, MD
1. Prospective comparison of radial forearm free flap donor site healing using negative pressure dressing and
immobilization splint.
2. Prospective comparison of postoperative pain following tonsillectomy using monopolar cautery vs tissue
welder.
Brad deSilva, MD
1. Intraoperative EMG Findings and Voice Outcomes for Type I Thyroplasty
2. Treatment Outcomes for Patients with Exercise and Irritant-Induced Paradoxical Vocal Fold Motion
3. Transoral Peritonsillar Ultrasound for ER Patients with Peritonsillar Abscess
Kris Jatana, MD
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Identification of circulating tumor cells in squamous cell carcinoma of the head and neck
Identification of circulating tumor cells in adenoid cystic carcinoma
Neonatal upper airway hamartomas
Efficacy of upper airway surgery in Prader-Willi patients
Radiographic findings in pediatric periorbital cellulitis
Transtracheal repair of traumatic tracheoesophageal fistula
Role of balloon dilation in neonatal choanal atresia repair
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Long-term outcomes of nasal CPAP use in the NICU setting
Post-extubation laryngoscopy findings in low birth weight neonates
Use of autologous fat grafting in pediatric tympanoplasty
Mechanisms of esophageal button battery injury and development of vocal cord paralysis
Nasopharyngeal rhinosporidiosis: A rare entity in the United States.
Velopharyngeal dysfunction in 22q deletion patients
Bhavna Kumar
1. Evaluation of Differences in Tumor Biology of Head and Neck Cancer.
Head and Neck cancer is the 6th leading cancer by incidence worldwide and arises in the oral cavity,
oropharynx, larynx, hypopharynx and nasopharynx. Although 95% of head and neck cancers are squamous
cell carcinomas, there is considerable heterogeneity amongst them suggesting the existence of molecularly
different subgroups. There subgroups differ both at the molecular level as well as the clinical level. Most
prominent among the subgroups include those that are caused by smoking and alcohol use versus those that
are caused by infection with human papillomavirus (HPV). Most patients with HPV positive tumors respond
better to chemoradiation therapy and have better prognosis as compared to patients with HPV negative
tumors. In addition, response to therapy also depends on the primary site involved. Unraveling of the
biological characteristics of the heterogeneous subgroups could lead to the development of novel and
personalized therapies for the treatment of patients with head and neck cancer ultimately translating into
better survival with less toxicity and morbidity. In order to achieve this, we have built tissue microarrays
(TMAs) from archived tumor tissue from patients with oropharyngeal cancer. These TMAs will be used to
analyze the expression of tumor specific as well as tumor-associated biomarkers. The expression of the
biomarkers will be linked to the clinical as well as demographic characteristics of the patients to delineate
aggressive versus non aggressive cancers, to predict outcome and identify the most appropriate treatment
strategy.
Pawan Kumar, PhD
1. Role of IL-6 in head and neck cancer progression and metastasis.
Distant metastases in head and neck cancer almost invariably herald a poor prognosis with an average
survival of 6 months and treatment is usually palliative. Five year survival rates for early stage localized head
and neck cancers are over 80% but this drop to 40% where disease has spread to neck nodes, and to below
20% for patients with distant metastatic disease. Uncontrolled cell proliferation and angiogenesis are key
characteristics of initiation and early growth of epithelial origin cancers. However, it is the subsequent
acquisition of motility and invasiveness that leads to metastatic dissemination of these tumor cells. Although
our understanding of the biology of tumor cells has considerably improved in recent years, similar growth in
the knowledge of the molecular events that promote tumor cell release from the primary tumor and metastasis
to distal sites have not been achieved. Understanding the molecular mechanisms that contribute to tumor cell
release and acquisition of anoikis resistance can greatly help us design new strategies to block distal tumor
metastasis. In this project, we propose to examine the molecular mechanisms that mediate IL-6-induced
epithelial-mesenchymal transition (EMT), anoikis resistance and expansion of cancer stem cells (CSCs). In
addition, we will use clinical samples from head and neck cancer patients to further examine if serum/tumor
IL-6 levels correlate with circulating tumor cells (CTCs) and tumor metastasis.
2. Role of tumor-associated endothelial cells in head and neck cancer progression and metastasis.
The tumor microenvironment plays a critical role in tumor growth and tumor metastasis to distal organs. It
is well established that tumor angiogenesis plays an important role in tumor progression. In addition, recent
studies have shown that tumor-associated endothelial cells are dysfunctional and may contribute to tumor
metastasis and resistance to anti-tumor therapies. However, the precise role tumor-associated endothelial
cells play in promoting tumor growth and tumor metastasis is poorly understood. In this project, we propose to
examine if tumor cell binding to tumor associated endothelial protect these tumor cells against anoikis and
chaperone them to distal sites.
3. Identifying key microRNA signatures that underline the aggressive head and neck cancer phenotype.
Oral and oropharyngeal cancers are among the most common cancers worldwide affecting nearly
500,000 people each year. Even with extensive surgery and full course irradiation the survival rates,
particularly for oral cancer are worse than for breast cancer, malignant melanoma and lymphoma. Recently
developed chemoradiation treatment protocols for head and neck cancer are improving survival for advanced
larynx and oropharynx cancer patients for the first time in nearly forty years. However, these treatment
approaches have not been successful in a subset of patients with oropharynx cancer and most with oral
cancer. These remain the most difficult of the head and neck cancers to manage. Thus, it is important to
better understand the biological factors that are responsible for the aggressiveness of this disease and to find
the most appropriate treatment for each patient based on the biology of their tumor. We have identified a
panel of microRNA (miR) that is dysregulated in head and neck cancers. In this project, we will use both in
vitro and in vivo models to examine the role of these miRs in head and neck cancer progression.
4. Targeted therapies for head and neck cancers.
Treatment of advanced head and neck tumors remains a challenging clinical problem, due to the
persisting high rate of local and distant failure. Currently, many advanced stage head and neck tumors are
being treated with concurrent chemoradiation therapy but this treatment regimen is often associated with
significant toxicity. Recent research efforts have attempted to develop targeted tumor-specific therapies to
minimize normal tissue toxicity but maximize therapeutic benefits. We have recently shown that IL-6 is a key
chemokines that play an important role in head and neck cancer growth and metastasis. IL-6 predominantly
mediates its biological function via the activation of JAK-STAT3 signaling pathway. We are collaborating with
Dr. Chenglong (College of Pharmacy) to develop novel IL-6 inhibitors (MDL-5 and MDL-16) to targets head
and neck cancers. In addition, we are collaborating with Dr. Kuppusamy’s group to develop a new class of
compounds (difluoro-diarylidenylpiperidone -DAPs) that selectively block STAT3 function. We have also
identified another potential target (survivin), particularly for head and neck cancers that have developed
chemo-resistance. In our study, we have observed significant elevated levels of survivin in head and neck
cancer cell lines as compared normal oral keratinocytes. Interestingly, acquisition of cisplatin resistance by
CAL27-PT cells resulted in further increase of survivin expression as compared to the parental cell line.
Therefore, we hypothesize that targeting of survivin protein in advanced HNSCC could reverse the resistant
phenotype in tumor cells thereby enhancing the therapeutic efficacy cisplatin treatment. We propose to use
both in vitro and in vivo preclinical models to test the efficacy of small molecule inhibitors (MDL; IL-6, DAP;
STAT3 and YM155; survivin) either as a single agent or in combination with cisplatin treatment.
Bomjun Kwon, PhD
1. Perceptual consequences of electric hearing through cochlear implants
(subtitle: development of novel stimulation methods and validation)
Jas Lang, PhD
1. Identification and Characterization of Cancer Stem Cells in HNSCC
The overall 5-year survival rate for head and neck squamous cell carcinoma (HNSCC) is approximately
50% and this rate has not changed significantly in the past 20 years. Such a poor prognosis is partly due to
the propensity of the disease to spread to regional lymph nodes and distant metastatic sites and due to the
high rate of loco/regional recurrence (50-60%) despite initially successful therapeutic intervention. For cancer
overall, it has been suggested that continuing metastatic spread and recurrence post-therapy may be due to
the presence of a small population of cancer cells within the primary tumor that is resistant to therapy and that
can eventually repopulate the tumor. These cells are thought to comprise Cancer Stem Cells (CSC) [aka
Cancer Initiating Cells (CIC)] and tumor cells that have undergone Epithelial Mesenchymal Transition (EMT).
For all cancers, including HNSCC it is therefore important to both identify and characterize such cells.
Successful therapy may necessitate combined strategies to target simultaneously the bulk of the tumor cells
(CIC/EMT-negative cells) and the CIC/EMT-positive cell population.
Tumor cell lines are useful surrogates for human tumors, allowing functional investigation of the pathways
that are deregulated during the development of cancer and allowing study of the response of tumor cells to
therapeutics. A number of cell lines have previously been established from squamous cell carcinoma of the
head and neck (HNSCC), and study of these cell lines and their response to drugs has provided valuable
information. However, pathological and clinical information associated with such cell lines is sparse and their
long term culture as direct monolayers on plastic surfaces brings into question whether these lines are a true
representation of the original tumors from which they are derived. In an attempt to address these concerns,
we are developing a cell culture system to establish new cell lines directly from HNSCC tumor specimens
obtained from patients undergoing curative resection for HNSCC in the James Cancer Hospital. This
resource, comprising 20 novel HNSCC cell lines to date, the original matched tumor tissue from which the cell
lines are derived, corresponding normal tissue, and an existing HNSCC tumor bank containing over 1000
fresh frozen specimens of HNSCC, forms the basis for study of the gene alterations associated with the
development of cancer stem cells. We will attempt to isolate CSC from our established cell lines, study the
gene alterations responsible for their development and validate these studies by determining whether such
alterations can also be found in the original tumor specimens.
Meredith Merz, MD
1. Comparison of paranasal sinus volume in adults with cystic fibrosis and normal adults.
2. Pediatric Tracheostomy: A 10 year review at a tertiary children's hospital.
3. Hearing loss after concussion.
Susan Nittrouer, PhD
1. Early Development of Children with Hearing Loss
2. Ontogeny of Segmental Speech Organization
Quintin Pan, PhD
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Role of PKCε in aggressive HNSCC
Design and development of PKCε inhibitors for HNSCC
Regulation of cancer initiating cell self-renewal and chemoresistance
Role of HPV on cancer initiating cell phenotype
Design and development of p300 inhibitors to target cancer initiating cells
Mechanism of EGFR dysregulation in HNSCC
Development of ESX inhibitors to target EGFR/Her2 expression in HNSCC
Role of microRNAs in HNSCC development and progression
Design and development of nanoparticles as a carrier system to deliver anti-cancer therapeutics
Matthew Old, MD
1. Herpes oncolytic viral therapy for head and neck cancers
2. PRMT5 expression and targeted inhibition in head and neck squamous cell carcinoma
3. Clinical trials:
 Principle Investigator: Randomized, Double-blind, Multicenter Two-Stage Adaptive Phase 3 Study of
Intravenous Administration of REOLYSIN® (Reovirus Type 3 Dearing) in Combination with Paclitaxel
and Carboplatin versus the Chemotherapy Alone in Patients with Metastatic or Recurrent Squamous
Cell Carcinoma of the Head and Neck (SCCHN) who have Progressed on or after Prior PlatinumBased Chemotherapy. Open of trial pending
 Principle Investigator: Randomized, prospective trial of post-operative hyperbaric oxygen after head
and neck surgery following radiation or chemoradiation. Trial being developed.
 Co-investigator of OSU-10128: Pilot studies with Newly Diagnosed Squamous Cell Carcinoma of the
Oropharynx
 Co-Investigator of OSU-0497: A Phase Ib Pilot Study Evaluating Oral Administration of Freeze-Dried
Black Raspberries in Pre-Surgical Patients with Oral Squamous Cell Carcinoma
 Co-Investigator of OSU-06132: A Pilot Study Evaluating Long-Term Oral Administration of FreezeDried Black Raspberries in Post-Surgical Appalachian Oral Cancer Patients.
 Co-Investigator of OSU-07085: Food Based Modulation of Biomarkers in Human Tissues at High-Risk
for Oral Cancer.
 Co-Investigator of OSU-07061: A Pilot Study Assessing Transoral Robotic Surgery (TORS) for Oral
and Laryngopharyngeal Benign and Malignant Lesions Using the Da Vinci Robotic Surgical System.
 Co-Investigator of OSU-08149: A Phase 3, Prospective, Open-Label, Multicenter Study of
Lymphoseek® as Lymphoid Tissue Targeting Agent in Patients With Known Cutaneous or Mucosal
Head and Neck Squamous Cell Carcinoma Who Are Undergoing Lymphadenectomy
 Co-Investigator of OSU-08095: The Role of Direct Visual Fluorescence in Oral Examination
Enver Ozer, MD
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Prospective TORS Clinical Trial
TORS and Non surgical treatments for oropharynx cancer: a QOL comparision
Comparison of reconstructive techniques in head and neck cancer
Carotid artery invasion; pathologic and molecular determinants
Adenoid cystic cancer and hormone receptors
PET CT characteristics of head and neck cancer
Antoine Shahin, PhD
1. Neural mechanisms for word segmentation in normal hearing individuals and individuals with hearing loss.
2. Development of electrophysiological response to speech.
3. The brain response to speech in individuals with cochlear implants (a collaboration with Dr. Welling and
Dr. Moberly).
HuaHua Tong, PhD
1. Research activities in Tong’s lab
Spn is one of the primary pathogens of OM. Despite advances that have been made in Spn OM research
in the last decade, much more remains to be learned about the otological immunology for better
understanding of the pathogenesis of OM. The long-term objectives of our research projects are to evaluate
host-bacterial cell interrelationship with the purpose of developing strategies for blocking or immunizing
against this interaction and thus preventing the development of OM.
2. On-going investigations include:
 Assessment of the complement activation in the middle ear epithelium during Spn infection.
 Defining the role of the specific complement pathway activation in the middle ear defense against Spn
using a complement deficient mice.
 Evaluating the role of the complement system in the middle ear against Spn with an antecedent
influenza A virus infection in the mouse model of pneumococcal OM.
 Together our studies will expand our understanding of the role of the complement system in middle ear
innate immunity during Spn OM and may identify new targets for therapeutic intervention.
D. Bradley Welling, MD
1. Basic Science of Pathway Activation in Vestibular Schwannomas and Meningiomas (Welling, Chang)
2. Potential Chemotherapeutic Agents (Natural Compounds, AR42) for the Treatment of NF2-Associated
Schwannoma and Meningioma (Welling, Chang)
3. Quality of Life Outcomes in Patients with Vestibular Schwannomas (Welling)
4. Treatment of Chronic Tympanic Membrane Perforations with Fibroblast Growth Factor-1 (Welling)
5. Revision Stapedectomy: The Ohio State University Medical Center Experience and A Literature Review
(Welling)
6. Rates of Spontaneous Miscarriages and Neural Tube Defects in Patients with NF2 (Welling, Chang)
7. Utilizing Magnetic Resonance Imaging and Auditory Brainstem Response to Assess Schwannoma and
Meningioma Growth in Mice (Welling, Chang)
8. Novel Treatment of Vestibular Schwannomas and Meningomas in the Mouse Xenograft Model (Welling,
Chang)
Gregory Wiet, MD
1. Virtual temporal Bone Surgery: Defining and Translating Standardized Metrics.
Description: Further development of a computer based virtual reality temporal bone bone for training and
assessing technical performance in temporal bone surgery. See
http://www.osc.edu/research/Biomed/projects/vtbone/index.shtml.
2. Complement in Streptococcus pneumoniae otitis media.
Description: project performed in conjunction with Dr. Hua Hua Tong, this project focuses on the role of
complement in human subject with otitis media.
3. Clinical pediatric otolaryngology.
Description: Various clinical projects such as case reports, retrospective reviews, etc. with emphasis on
pediatric otolaryngology.