University of Pittsburgh Faculty Research Information
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University of Pittsburgh
Faculty Research
Information
02/29/2012
Page 1
Cuneyt M. Alper, MD
Professor of Otolaryngology
University of Pittsburgh School of Medicine
Children’s Hospital of Pittsburgh of UPMC
Division of Pediatric Otolaryngology
Director, Pediatric Otolaryngology Fellowship Program
Children’s Hospital of Pittsburgh of UPMC
4401 Penn Avenue
Faculty Pavilion, 7th floor
Pittsburgh, PA 15224
Phone: 412-692-8577
Fax: 412-692-6074
Email: Cuneyt.alper@chp.edu
Email: alperc@pitt.edu
Links:
CV: Cuneyt M. Alper, MD
Research Description:
Ear, Middle
Eustachian Tube
Otitis Media
Otitis Media with Effusion
Otitis Media, Suppurative
Common Cold
Respiratory Tract Infections
Page 2
Education:
MD., Hacettepe University, Ankara, Turkey
Residency, Kartal Training and Research Hospital, Istanbul, Turkey
Fellowship, Children’s Hospital of Pittsburgh, Division of Pediatric Otolaryngology
Recent Publications:
Alper CM, Kitsko DJ, Swarts, JD, Martin B, Yuksel S, Cullen Doyle BM, Villardo RJ, Doyle
WJ. Role of the mastoid in middle ear pressure regulation. Laryngoscope, 2011; Feb:121(2): 404-
8.
Silva RC, Simons JP, Chi, DH, Yellon RF, Alper CM. Endoscopic treatment of plastic
bronchitis. Arch Otolaryngol Head Neck Surg, 2011; Apr:137(4): 401-403.
Swarts JD, Alper CM, Mandel EM, Villardo RJ, Doyle WJ. Eustachian tube function in adults
without concurrent ear disease. Ann Otol. Rhinol Laryngol, 2011Apr:120(4): 220-5.
Doyle WJ, Swarts, JD, Banks J, Yuksel S, Alper CM. Transmucosal O2 and CO2 exchange rates
for the human middle ear. Auris, Nasus, Larynx. 2011 Dec:38(6) 684-91. (Epub 2011 Feb 16).
Alper CM, Losee JE, Mandel EM, Seroky JT, Swarts DJ, Doyle WJ. Post-palatoplasty
Eustachian tube function in young children with cleft palate. Cleft Palate Cranio J, 2011 Jul 8
(Epub ahead of printing).
Page 3
Carey D. Balaban, PhD
Professor of Otolaryngology, University of Pittsburgh
Professor of Neurobiology, University of Pittsburgh
Professor of Communication Sciences and Disorders, University of Pittsburgh
Professor of Bioengineering, University of Pittsburgh
Director, Center for National Preparedness, University of Pittsburgh
Co-Director, Consortium for Integrative Scientific Convergence, University of Pittsburgh and
Potomac Institute for Policy Studies
Academic Fellow, Potomac Institute for Policy Studies, Arlington, VA
Eye & Ear Institute
Suite 107
203 Lothrop Street
Pittsburgh, PA 15213
Phone 412.647.2298
Fax 412.647.1080
Email: balabancd@upmc.edu
Links
PubMed:
NIH RePorter:
CV: Carey Balaban, PhD
Research Description:
Anatomy, neurophysiology, and neurochemistry of vestibular function.
Research theme: Behavioral/Systems/Cognitive
Areas of concentration: Balance and Vestibular Function; Molecular Responses of Inner Ear to
Toxin and Blast Injury; Psychophysics, Simulation and Modeling
The primary goal of Dr. Balaban's research has been to develop a rational basis for understanding
the neurobiology of the vestibular system so that new therapies for vestibular disorders can be
designed. This goal is approached by: (1) identifying the organization of central vestibular
circuits that mediate autonomic and somatic motor responses to vestibular stimulation; (2)
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identifying neurotransmitters and intracellular signal transduction proteins that are important in
these brain circuits; (3) examining the role of these biochemical constituents in responses to
challenges from toxins and mechanical (blast) injury; and (3) identifying contributions of these
mechanisms to the clinical linkage among balance disorders, anxiety disorders (panic with
agoraphobia) and migrainous vertigo. These studies have a strong translational component
through interactions with Drs. Joseph Furman (Otolaryngology), Rolf Jacob (Psychiatry), Dawn
Marcus (Neurology), Susan Whitney (Physical Therapy, SHRS), John Durrant (Communication
Sciences & Disorders, SHRS) and Mark Redfern (Bioengineering).
Current studies include: (1) analysis of connectional and neurochemical parallels between
ascending vestibular and nociceptive pathways, (2) proteomic, lipidomic, genomic,
neurochemical and histopathological analyses of repair processes after blast-induced mild
traumatic brain injury that explain headache and dizziness in patients, (3) studies of changes
metabolic protein and mRNA expression in the inner ear ganglion cells after chemical challenges
to the inner ear; (4) quantitative modeling studies genetic and neural bases for human subjective
responses to pain and (5) translating neural principles into operations research and
neurotecnological approaches for homeland security and defense applications (through the Center
for National Preparedness, Potomac Institute for Policy Studies and collaborations with the
corporate sector).
Trainees in Dr. Balaban's laboratory will have the opportunity to apply a variety of anatomical,
neuropharmacological, electrophysiological and cellular/molecular methods to study vestibular
function. These methods include state-of-the-art tract tracing methods, immunohistochemical
methods, quantitative PCR, in situ hybridization, computer, electrophysiology, and a variety of
standard and non-standard mathematical modeling and signal analysis methods. Intellectual
training includes exposure to regular group meetings that discuss translation of basic findings into
clinical practice and other cross-disciplinary applications.
Education
PhD, University of Chicago (1979)
Postdoctoral, University of Tokyo, (1979-1982)
Recent Publications
McCandless CH, Balaban CD. Parabrachial nucleus neuronal responses to off-vertical axis
rotation in macaques. Exp Brain Res 202(2): 271-90, 2010
Ahn SK, Balaban CD. Distribution of 5-HT1B and 5-HT1D receptors in the inner ear. Brain Res.
1346:92-101, 2010.
Balaban CD, Jacob RG, Furman JM. Neurologic bases for comorbidity of balance disorders,
anxiety disorders and Migraine: neurotherapeutic implications. Expert Rev Neurother.11:379-
394, 2011.
Jeffrey S. Mogil*, Robert E. Sorge, Michael L. LaCroix-Fralish, Shad B. Smith, Anny Fortin,
Susana G. Sotocinal, Jennifer Ritchie, Jean-Sebastien Austin, Ara Schorscher-Petcu1, Kara
Melmed, Jan Czerminski, Rosalie A. Bittong, J. Brad Mokris, John K. Neubert, Claudia M.
Campbell, Robert R. Edwards, James N. Campbell, Jacqueline N. Crawley, William R. Lariviere,
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Margaret R. Wallace, Wendy F. Sternberg, Carey D. Balaban, Inna Belfer, and Roger B.
Fillingim. Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment
interaction, Nature Neuroscience, doi:10.1038/nn.2941 , 2011.
Vardit Rubovitch, Meital Ten-Bosch, Ofer Zohar, Catherine R.Harrison, Catherine Tempel-
Brami,, Elliot Stein, Barry J. Hoffer, Carey D. Balaban, Shaul Schreiber, Wen-Ta Chiu, Chaim
G. Pick. A Mouse Model of Blast-Induced mild Traumatic Brain Injury, Experimental
Neurology, 232:280-289, 2011
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Charles D. Bluestone, MD
Distinguished Professor of Otolaryngology
Past Eberly Professor of Otolaryngology and Director of Pediatric Otolaryngology
Department of Otolaryngology
Children’s Hospital of Pittsburgh of UPMC
Department of Pediatric Otolaryngology
Children’s Hospital Drive
45th and Penn Ave.
Faculty Pavilion 7th Floor
Pittsburgh, PA. 15201
Phone 412-692-5902
Fax: 412-692-6075
Email bluecd@chp.edu
Links
PubMed
NIH RePorter
CV: Charles Bluestone, MD
Research Description:
Dr. Bluestone is currently involved with the role evolution plays in diseases and disorders of
infants and children, primarily otitis media. (See below, Recent Publications) He is also involved
with Eustachian tube testing of children and adults in the Eustachian tube function laboratories at
the Children’s Hospital of Pittsburgh of UPMC. Another ongoing research project involves a
potential animal model, Cavalier King Charles Spaniel, which has a greater than 50% incidence
of chronic otitis media effusion. Research being conducted with his colleagues in this animal
involves histopathology of the middle-ear cleft in cadavers, and Eustachian tube function tests in
live animals, conducted at the Ohio State University School of Veterinary Medicine in Columbus
Ohio. He also is involved with his research colleagues in measurements of crania from the
American Museum of Natural History in New York City, which is attempting to determine if
there are osteological differences in the skull base and Eustachian tube bony landmarks, as well
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as mastoid evidence of otitis media in the morphology of the mastoid gas cell system, in different
racial groups in which there has been reported to be varying degrees of incidence of otitis media.
Some aspects of his current research described above could be potential projects for residents.
Education:
University of Pittsburgh, BS (1954)
University of Pittsburgh, MD (1958)
Residency in Otolaryngology
University of Illinois School of Medicine (1962)
Recent Publications
Lim DJ, Bluestone CD, Casselbrant ML, eds. Recent Advances in Otitis Media: Report of the
Eighth Research Conference. Ann Otol Rhinol Laryngol 2005;194(No.1;Part 2) ( Supplement
194):1-160.
Bluestone CD. Impact of evolution on the Eustachian tube. Laryngoscope. 2008;118(3):522-527.
Bluestone CD. Galapagos: Darwin, Evolution and E.N.T. Laryngoscope, 2009;119(10):1902-5.
Casselbrant ML, Mandel EM, Rockette HE, Kurs-Lasky M, Fall PA, Bluestone CD.
Adenoidectomy for otitis media with effusion in 2-3 year-old children. Int J Pediatr
Otorhinolaryngol 2009;73(12):1718-1924.
Bluestone CD. Swarts JD. Human evolutionary history: consequences for the pathogenesis of
otitis media. Otolaryngol Head Neck Surg. 2010 Dec;143(6):739-44.Epub 2010 Oct 25.
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Margaretha L. Casselbrant, MD, PhD
Eberly Professor of Pediatric Otolaryngology
University of Pittsburgh School of Medicine
Director, Division of Pediatric Otolaryngology
Children’s Hospital of Pittsburgh of UPMC
Children’s Hospital of Pittsburgh of UPMC
4401 Penn Avenue
Faculty Pavilion, 7th Floor
Pittsburgh, PA 15224
Links
CV: Margaretha L. Casselbrant, MD, PhD
Research Description:
Dr. Casselbrant’s main research interest is focused on otitis media and she has conducted
numerous clinical trials and studies assessing the efficacy of medical and surgical treatments for
otitis media. Dr Casselbrant has also performed balance studies in children to obtain normative
age related rotational and posturography data and assess the effect of otitis media on balance by
following a group of children with documented history of otitis media longitudinal from 3 years
through 9 years of age with yearly examinations.
Dr. Casselbrant has also investigated the genetic aspects of otitis media. The first study which
enrolled mono- and dizygotic twins demonstrated a significantly higher concordance rate for the
MZ twins compared to the DZ twins with a very high hereditary estimate (74). A genome-wide
linkage scan in 500 families with two children having had tympanostomy tube inserted has been
just been completed, which demonstrates evidence of susceptibility loci within the 17q12 and
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10q22.3 regions for otitis media. We are in the progress of submitting a RO1 to further evaluate
the genetic contributions in otitis media
Dr. Casselbrant is the PI on the ongoing study “Eustachian Tube Growth and Development:
Anatomy/Function’ which is a part of Dr Doyle’s Program Project entitled “Middle Ear Pressure
Regulation in Health and Disease”. This longitudinal study will test the hypothesis that age-
related changes in the ET-paratubal muscle vector relationships are reflected in more efficient
ET-function and, by consequence, a reduction in otitis media risk. The children are examined
with non-invasive anthropometric measures, cephalometrics and MRI (in subset). ET-function
will be assessed in a pressure chamber if the tympanic membrane is intact.
Dr. Casselbrant is also a Co-I on the ongoing study “Social and Psychological Risk for Infectious
Illness” (PI Dr Cohen), which uses an upper respiratory infectious disease paradigm as a model to
investigate the potential influence of psychosocial factors (stressful events, social networks and
support, interpersonal conflicts and strains, and social disposition) on infections, viral induced
inflammatory processes and disease expression. The subjects (adults) are followed prospectively
for assessment of their social environment and they are also “cloistered” for inoculation with a
virus that causes a mild common cold. During this time they are closely monitored for infections
and illness expression.
Education:
BA University of Lund, Lund, Sweden, 1964-1965
MD University of Lund, Lund, Sweden, 1969-1973
PhD University of Lund, Lund, Sweden, 1975-1979
Internship University of Lund, Malmo, Sweden, 1973-1974 (18 months)
Residency University of Lund, Malmo General Hospital, Malmo, Sweden, 1975-1978
Fellowship University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh,
Pittsburgh, PA, 1980-1982
Recent Publications:
Rodriguez KD, Sun GH, Mandel EM, Casselbrant ML, Pike F, Chi DH. Post-tonsillectomy
bleeding in patients with von Willebrand disease. Otolaryngol Head Neck Surg 2010;
142(5):715-721. http://www.ncbi.nlm.nih.gov/pubmed/20416462
Davidson HC, Stapleton AL, Casselbrant ML, Kitsko DJ. Perioperative incidence and
management of hyponatremia in vWD patients undergoing adenotonsillectomy. Laryngoscope
2011; 121(7):399-403. http://www.ncbi.nlm.nih.gov/pubmed/21647890
Sale MM, Chen WM, Weeks DE, Mychaleckyj JC, Hou X, Marion M, Segade F, Casselbrant
ML, Mandel EM, Ferrell RE, Rich SS, Daly KA. PLoS One 2011; 6(8):e22297.
http://www.ncbi.nlm.nih.gov/pubmed/21857919
Casselbrant ML, Mandel EM, Seroky JT, Swarts JD, Doyle WJ. A pilot study of the ability of
the forced response test to discriminate between 3-year-old children with chronic otitis media
with effusion or with recurrent acute otitis media. Acta Otolaryngol 2011; 131(11):1150-4.
http://www.ncbi.nlm.nih.gov/pubmed/21846295
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10Cohen MS, Mandel EM, Redfern MS, Furman JM, Sparto PJ, Casselbrant ML. Tympanostomy
tube placement and vestibular function in children. Otolaryngol Head Neck Surg 2011;
145(4):666-672. http://www.ncbi.nlm.nih.gov/pubmed/21676943
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11David H. Chi, MD
Assistant Professor of Otolaryngology
University of Pittsburgh School of Medicine
Director, Hearing Center
Division of Pediatric Otolaryngology
Children’s Hospital of Pittsburgh of UPMC
4401 Penn Avenue
Faculty Pavilion, 7th floor
Pittsburgh, PA 15224
Phone: 412-692-8577
Fax: 412-692-6074
Email: david.chi@chp.edu
Links
CV: David H. Chi, MD
Research Description:
Interests are in the evaluation and treatment of pediatric sensorineural hearing loss. Basic science
research interest encompasses understanding the mechanisms of neural circuit development in
auditory neuropathy
Education:
BS, Biomedical Sciences/Sociology, University of Michigan
MD., University of Michigan
Surgical Internship, University of Virginia
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12Residency, Otolaryngology, University of Virginia
Fellowship, Children’s Hospital of Pittsburgh of UPMC, Division of Pediatric Otolaryngology
Recent Publications:
Kitsko DJ, Chi DH. Coblation removal of large suprastomal tracheal granulomas. Laryngoscope
2009 Feb;119(2):387-9
Cohen MS, Zhuang L, Simons JP, Chi DH, Maguire RC, Mehta DK. Injection laryngoplasty for
type 1 laryngeal cleft in children. Otolaryngol Head Neck Surg. 2011 Feb 4 [Epub ahead of print]
Silva RC, Chi DH. Successful management of a tracheo-innominate fistula in a 7-year-old child.
Int J Pediatr Otorhinolaryngol. 2010 Aug;74(8):946-8.
Rodriguez KD, Sun GH, Pike F, Mandel EM, Casselbrant ML, Chi DH. Post-Tonsillectomy
bleeding in children with von Willebrand disease: A single-institution experience.
Otolaryngology – Head and Neck Surgery, 2010 May;142(5):715-21
Dunklebarger J, Branstetter B, Lincoln A, Sippey M, Cohen M, Gaines B, Chi DH. Pediatric
Temporal Bone Fractures: Current trends and comparison of classification schemes.
Laryngoscope. Accepted.
Silva RC, Simons JP Chi DH, Yellon RF, Alper C. Endoscopic Management of Plastic
Bronchitis. Archives of Otolaryngology-Head & Neck Surgery. 2011 Apr; 137(4): 401-3.
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13Joseph E. Dohar, MD, MS, FAAP, FACS
Professor of Otolaryngology
University of Pittsburgh School of Medicine
Clinical Director
Pediatric Voice, Resonance, & Swallowing Center
RESEARCH DESCRIPTION:
Dr. Dohar is actively involved in research efforts to improve healing of the skin and mucosa of the ear, nose and
throat. As a collaborator of the ENT Wound Healing Research Program, Dr. Dohar is working with talented
graduate students, residents and postdoctoral fellows and has a close collaboration with other faculty members,
notably Patricia A. Hebda, Ph.D., the Director of the ENT Would Healing Research program and research
partner. The goal of their research team is to establish a multifaceted program encompassing preclinical and
clinical projects. The fundamental purpose is to develop new, biologically driven therapeutic modalities to
promote and optimize wound healing and tissue regeneration of the upper aerodigestive system. To achieve this
goal they have ongoing projects based on:
characterization of regenerative, or scarless, fetal wound healing
cell therapy and tissue engineering for laryngotracheal mucosa
animal and tissue culture model systems for airway injury
Another component of their research involves characterization of the fibrotic fibroblast phenotype as exhibited
in connective tissue scars, such as keloids and hypertrophic scars in the skin and stenoses of the airway. The
group is pursuing this study of fibrotic healing with scar formation in children and adults in contrast to the
scarless regenerative healing of fetal connective tissues of skin and airway mucosa.
The group is also investigating the role of inflammation in the pathogenesis of Otitis media, focusing on the
adverse effects of middle ear fluid evoked by Eustachian tube dysfunction and resultant negative pressure. Even
in the absence of bacterial or viral infection, the fluid produced in response to negative pressure contains
inflammatory mediators that can induce structural changes over the course of weeks and months.
As Medical Director of the Pediatric Voice, Resonance, & Swallowing Center, Dr. Dohar maintains the oldest
clinical research registry in the nation. A variety of retrospective and prospective clinical investigations
pertaining to pediatric dysphonia, dysphasia, and velopharyngeal insufficiency are ongoing. Also, pediatric
secretion control and salivary aspiration are focused areas of clinical investigation.
Finally, Dr. Dohar has a long clinical-standing interest in the management of chronic suppurative otitis media
and otorrhea. Current ongoing clinical investigations include epidemiology, natural history, microbiologic
changes, and new ototopical antimicrobial drug development.
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14Umamaheswar Duvvuri, M.D., Ph.D.
Assistant Professor of Otolaryngology, Division of Head and Neck Surgery
University of Pittsburgh School of Medicine
Director, Robotic Head and Neck Surgery, VA Pittsburgh Health System
Suite 500 EEI
200 Lothrop Street
Pittsburgh, PA 15213
Phone: 412-647-2117
Email: duvvuriu@upmc.edu
Fax: 412-647-2080
Links
PubMed
NIH RePorter
CV: Umamaheswar Duvvuri, M.D., Ph.D.
Research Description:
Dr. Duvvuri is currently investigating novel oncogenic pathways in head and neck squamous cell
carcinomas. We use a variety of molecular and imaging modalities to address these questions.
Active research projects include investigations of:
The role of a novel calcium-activated chloride channel (ANO1) in SCCHN
The signaling pathways activated by PlexinB1/Semaphorin4D in SCCHN
The interaction(s) between mesenchymal stem cells and SCCHN
Clinical & Translational Projects
Transoral anatomy three dimensional anatomy of the oropharynx and infra temporal fossa
Retrospective review of outcomes of robotic head & neck surgery
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15Education:
B.S.E., University of Pennsylvania, Bioengineering, 1996
M.S.E., University of Pennsylvania, Bioengineering, 1996
M.D., University of Pennsylvania, Medicine, 2002
Ph.D., University of Pennsylvania, Biophysics, 2002
Internship, General Surgery, University of Pittsburgh Medical Center, 2003
Residency, Otolaryngology, University of Pittsburgh Medical Center, 2006
Fellowship, Head & Neck Surgery, UT MD Anderson Cancer Center, 2008
Recent Publications:
Duvvuri U, Simental AA, Johnson JT, Ferris RL, Myers EN. (2006). Selective neck dissection
for the management of the N+ neck. Annals of Otolaryngology 115(11), 846-849.
Carrau RL, Kassam AB, Snyderman CH, Duvvuri U, Mintz A, Gardner P. (2006). Endoscopic
transnasal anterior skull base resection for the treatment of sinonasal malignancies. Operative
Techniques in Otolaryngology 17(2), 102-110.
Folbe A, Herzallah I, Duvvuri U, Bublik M, Sargi Z, Snyderman C, Carrau R, Casiano R.
Endoscopic endonasal resection of esthesioneuroblastoma: A multicenter study; 2009 January-
February, Vol. 23, No. 1:91-95.
Duvvuri U, Myers JN. (2009). Contemporary management of oropharyngeal cancer: Anatomy
and physiology of the oropharynx. Current Problems in Surgery; 2009, February: 46(2), 119-84.
Rivera-Serrano CM. Terre-Falcon R. Duvvuri U, “Combined approach for extensive
maxillectomy: technique development and cadaveric dissection.” Laryngoscope. 120 Suppl
4:S178, 2010.
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16Ann Marie Egloff, PhD, MPH
Assistant Professor
Department of Otolaryngology
University of Pittsburgh School of Medicine
W953 Biomedical Science Tower
200 Lothrop Street, Suite 500
Pittsburgh, PA 15213
Phone 412.648.9545
Fax 412.383.5409
Email egloffam@upmc.edu
Links
PubMed http: //www.ncbi.nlm.nih.gov/pubmed?term=Egloff%20AM
NIH RePorter http://projectreporter.nih.gov/reporter.cfm
CV: Ann Marie Egloff, PhD, MPH
Research Description:
Overview
The goals the Dr. Egloff’s research are to identify molecular characteristics including genetic
variants and acquired tumor alterations that contribute to the development and progression of
upper aerodigestive cancers with the ultimate aim of assessing risk, improving early disease
detection and identifying effective targeted therapies.
Projects
Genetic Polymorphisms and Head and Neck and Lung Cancer Risk:
The epidermal growth factor receptor (EGFR), the gastrin-releasing peptide receptor (GRPR) and
estrogen receptors (ER) are aberrantly overexpressed and activated in head and neck squamous
cell carcinoma (HNSCC) and lung cancers. Identifying EGFR, GRPR and/or ER genetic variants
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17that are associated with either HNSCC or lung cancer is a primary focus of ongoing research.
Identifying variants associated with these cancers will help to define patients who have increased
risk for these cancers and will provide important insights as to how these signaling components
contribute to the development and progression of these cancers. A large HNSCC case-control
cohort has been genotyped for candidate polymorphisms, and specific polymorphisms in EGFR
and ER have been identified to be associated with HNSCC. Similarly, candidate polymorphisms
have been evaluated in the EGFR-GRPR-ER signaling axis in lung cancer patients and cancer-
free controls and specific disease-associated polymorphisms identified. The laboratory is now
working to define the functional consequences of these cancer-associated variants.
HNSCC Tumor Alterations and Patient Prognosis:
Dr. Egloff’s laboratory is investigating clinically important relationships between inherited
genetic variation, tumor mutations and epigenetic alterations and patient survival. The laboratory
is working to define correlations between inherited genetic variants, altered tumor expression
profiles of EGFR-GRPR-ER signaling axis components and patient clinical outcomes. Molecular
studies of clinical specimens provide the underpinnings for these studies. Hypotheses stemming
from these studies can be further investigated using preclinical models of head and neck cancer.
This integrated approach using both clinical and preclinical research avenues provides for the
thorough investigation of clinically relevant hypotheses.
HNSCC Tumor Alterations and Response to Targeted Therapies
The EGFR-targeted antibody therapeutic, cetuximab, has been approved for the treatment of
HNSCC. Response rates to cetuximab in clinical trials have been modest, and as yet, tumor or
patient characteristics that identify tumors that will respond to cetuximab are undefined. In
addition to identifying tumor molecular characteristics that define tumors most likely to respond
to therapeutics in clinical development, the lab is working to identify effective combinations of
therapeutics and their predictive biomarkers.
The Src family kinases, which are involved in the EGFR-GRPR-ER axis cross-talk and
downstream signaling events, are a focus of these studies. A Phase II clinical trial in HNSCC
patients combining the Src family kinases and spectrum kinase inhibitor, dasatinib, with the
EGFR-targeted antibody therapeutic, cetuximab, is currently ongoing. Patient tumor and blood
samples are being collected in order to evaluate candidate blood and tumor characteristics as
biomarkers for response to treatment.
Although EGFR, GRPR, ER and Src family kinases are aberrantly activated in HNSCC, these
genes were not found to be mutated in the recent study describing mutations in a large collection
of HNSCC tumors. A non-candidate whole exome sequencing analysis of HNSCC performed by
University of Pittsburgh and Broad Institute researchers including Dr. Egloff identified several
novel genes as being significantly mutated. Among these significantly mutated genes was
Notch1, which has been reported to be expressed in the presence of EGFR inhibitors in some
cancers, suggesting a possible mechanism of EGFR-targeted therapy resistance. The lab has
begun work to define the roles of the observed Notch1 mutations in HNSCC and to assess their
role in responsiveness versus resistance to EGFR-targeted therapies using immortalized
keratinocytes and preclinical models of HNSCC. The long term goal of this project is to define
tumor-specific molecular characteristics that predict response to treatment and aid in the selection
of treatment most likely to benefit the individual patient.
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18Education:
B.S. (Cellular and Molecular Biology), University of Pittsburgh, 1988
Ph.D. (Molecular Biology and Genetics), Johns Hopkins University School of Medicine, 1999
M.P.H. (Epidemiology), University of Pittsburgh Graduate School of Public Health, 2005
Postdoctoral Fellow, National Human Genome Research Institute, 2001-2003
Postdoctoral Scholar, University of Pittsburgh School of Medicine, 2003-2006
Recent Publications:
Stransky N*, Egloff AM*, Tward A*, Kostic A, Cibulskis K, Sivachenko A, Kryukov G,
Lawrence M, Sougnez C, McKenna A, Ramos AH, Stojanov P, Carter SL, Voet D, Cortes M,
Auclair D, Saksena G, Guiducci C, Onofrio R, Parkin M, Romkes M, Weissfeld J, Seethala RR,
Wang L, Winckler W, Ardlie K, Gabriel SB, Myerson M, Lander ES, Getz G, Golub TR,
Garraway LA, Grandis JR. The mutational landscape of head and neck squamous cell carcinoma.
Science, 2011 Aug 26;333(6046): 1157-60. Epub 2011 Jul 28. PMID: 21798893. PMC Journal-In
Process. http://www.sciencemag.org/content/333/6046/1157.full
Egloff AM, Liu X, Gaither Davis AL, Trevelline BK, Vuga MM, Siegfried JM, Grandis JR,
Elevated Gastrin-Releasing Peptide Receptor mRNA expression in buccal mucosa is associated
with head and neck squamous cell carcinoma (HNSCC), in press Head and Neck, 2011.
Argiris A, Feinstein TM, Wang L, Yang T, Agrawal S, Appleman LJ, Stoller RG, Grandis JR,
Egloff AM. Phase I and pharmacokinetic study of dasatinib and cetuximab in patients with
advanced solid malignancies. Invest New Drugs, 2011 Sep 1. [Epub ahead of print]PMID:
21881918
Egloff AM, Grandis JR. Improving Response Rates to EGFR-Targeted Therapies for Head and
Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment
with Src Inhibitors.J Oncol. 2009;2009:896407. Epub 2009 Jul 14.PMID: 19636423, PMCID:
PMC2712676
Egloff AM, Rothstein ME, Seethala R, Siegfried JM, Grandis JR, Stabile LP. Cross-talk between
estrogen receptor and epidermal growth factor receptor in head and neck squamous cell
carcinoma. Clin Cancer Res. 2009 Nov 1;15(21):6529-40. Epub 2009 Oct 13.PMID: 19825947,
PMCID: PMC2783886
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19Berrylin June Ferguson MD
Director of the Division of Sino-nasal Disorders and Allergy
Professor
Department of Otolaryngology
University of Pittsburgh School of Medicine
Suite 11500
1400 Locust St.
Pittsburgh, PA 15219
Phone 412.232.8989
Fax 412.232. 3727
Email: fergusonbj@upmc.edu
Links
CV: Berrylin June Ferguson MD
Research Description:
Dr. Ferguson’s research is dedicated to understanding and developing diagnostic tools and
targeted therapies for patients with acute and chronic sinus disorders. A challenge in developing
targeted therapies for sinus disorders is the nonspecificity of symptoms and the heterogeneity of
disorders that are encompassed under the umbrella of chronic rhinosinusitis. In 2011, she
showed that fully a third of patients with strong symptoms of CRS, actually have no evidence of
sinusitis by endoscopy or radiography. (CID, 2011) Thus tools, such as cultures, either
endoscopic or nasopharyngeal that will better direct therapies such as antibiotics are an attractive
practical solution since it is so difficult to diagnose CRS by symptoms.
While antibiotics are commonly prescribed for both acute and CRS, little evidence supports this
practice. Dr. Ferguson is designing studies to limit the use of antibiotics to patients who have
cultures showing pathogenic bacteria in mucopurulent secretions. In acute sinusitis,
nasopharyngeal cultures show promise in directing therapy more appropriately, while in CRS,
studies are underway to assess the efficacy of culture directed antibiotic therapy. In 2007, she
showed that is CRS, endoscopic cultures changed antibiotic therapy in 50% of patients treated. In
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20a survey conducted in 20o9, both general otolaryngologists and those subspecialized in
Rhinology, took cultures but rhinologists took them in 50% of patients with purulent secretions,
compared to 34% of general otolaryngologists. Thus research in to best practice guidelines and
continued quality monitoring are also part of the research interests of the division of Sino-nasal
Disorders and allergy.
Fungal sinus manifestations have long been an interest of Dr. Ferguson, and she is internationally
recongnized for her expertise in this topic and has published a Clinics of North America devoted
to Fungal Sinusitis. The diagnosis of the correct manifestation of fungal sinusitis is imperative in
order to direct appropriate therapy.
Finally, Dr. Ferguson has published more extensively than anyone recently on the role of dental
infections causing maxillary sinusitis and continues to study role of newly introduced imaging
modalities such as cone beam CT, which is associated with 10% of the radiation dose of
traditional thin slice CT, in detecting dental causes of sinusitis.
Education:
AB (Biology and History and Philosophy of Science), Princeton University, 1977
M.D., Duke University School of Medicine, 1980
Internship, Department of Surgery, Duke University School of Medicine , 1981-82
Residency, Division of Otolaryngology, Duke University School of Medicine 1983-85
Research Fellow, Division of Otolaryngology, Duke University School of Medicine 1985
National Foundation of Infectious Disease Research Fellowship in Mycology, Duke University
School of Medicine 1986
Recent Publications:
Longhini A, Ferguson BJ. Clinical Aspects of Odontogenic Maxillary Sinusitis: A Case Series.
Allergy & Rhinology. Accepted for publication February 2011.
Ferguson BJ, Otto BA, Pant H. When surgery, antibiotics, and steroids fail to resolve chronic
rhinosinusitis. Immunol Allergy Clin North Am. 2009 Nov;29(4):719-32. Review.
Chakrabarti A, Denning DW, Ferguson BJ, Ponikau J, Buzina W, Kita H, Marple B, Panda N,
Vlaminck S, Kauffmann-Lacroix C, Das A, Singh P, Taj-Aldeen S, Kantarcioglu A, Handa K,
Gupta A, Thungabathra M, Shivaprakash M, Bal A, Fothergill A, Radotra B. Fungal
rhinosinusitis: A categorization and definitional schema addressing current controversies.
Laryngoscope. 2009 Sep;119(9):1809-18. Review
Sok JC, Ferguson BJ. Differential diagnosis of eosinophilic chronic rhinosinusitis. Clin Allergy
Immunol. 2007;19:69-85.
Cincik H, Ferguson BJ. The impact of endoscopic cultures on care in rhinosinusitis.
Laryngoscope. 2006 Sep;116(9):1562-8.
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21Robert L. Ferris, MD, PhD, FACS
Professor (Tenure), Vice-Chair for Clinical Operations
Chief of Division of Head and Neck Surgery
Departments of Otolaryngology, Radiation Oncology,
and of Immunology
Co-Leader, Cancer Immunology Program
University of Pittsburgh Cancer Institute
Eye & Ear Institute
200 Lothrop Street, Suite 500
Pittsburgh, PA 15213
Phone 412-647-2117
Fax 412-647-2080
Email ferrisrl@upmc.edu
Links
PubMed
NIH RePorter
CV: Robert Ferris, MD, PhD, FACS
Research Description:
Dr. Ferris’s laboratory is focused on understanding basic immunological mechanisms of the T
lymphocyte response to cancer, for the development of novel immunotherapeutic approaches to
head and neck tumors. Tumor vaccine clinical trials are currently underway and in new
strategies are in development. A wild type p53 peptide based vaccine is currently in the later
stages of accrual (15/24 patients vaccinated), and funded by the H&N SPORE P50 grant. We are
Page
22particularly interested in the immune response to human papillomavirus (HPV)-associated head
and neck cancer, which appears to be a distinct subgroup of head and neck squamous cell
carcinomas. Monitoring the successful immune effects of individuals treated with
immunotherapy is a major effort, in order to develop improved generations of vaccine
approaches. We are also studying tumor induced immune evasion, such as defective antigen
processing and presentation to subvert CTL recognition of tumors. Recently the immune
activating effects of the clinically efficacious EGFR-specific monoclonal antibody, cetuximab,
have shown induction of natural killer (NK) cell and T cell induction and activation of dendritic
cells (DC). We identified a novel EGFR853-861 peptide, recognized by cytotoxic T lymphocytes
(CTL) which is enhanced by cetuximab in vitro and in vivo in HNC patients.
Another area of study involves the promotion of tumor metastasis by a family of molecules called
chemokines. We are finding important roles for chemokine receptors in cancer metastasis. These
chemokines are small, secreted molecules that mediate homing and recruitment of immune cells
in response to inflammation, through a family of G-protein linked receptors. Overall these studies
are designed to identify the chemokines relevant to progression of HNC and to provide initial
data on their possible clinical utility as components of future vaccination therapies for HNC. In
addition his group is interested in developing immune/inflammatory biomarkers present in the
bloodstream for head and neck cancer detection and monitoring in populations at risk for cancer
recurrence and/or second primary tumors
Education:
B.A. (Chemistry with honors and distinction) University of North Carolina at Chapel Hill, 1990
M.D. Johns Hopkins Medical School, Baltimore, MD, 1995
Ph.D. (Immunology) Johns Hopkins Medical School, Baltimore, MD, 1998
Internship (Surgery) Department of General Surgery, Johns Hopkins Hospital Baltimore, MD,
1996
Residency (Otolaryngology Head and Neck Surgery) Johns Hopkins Hospital Baltimore, MD,
2000
Chief Residency (Otolaryngology, Subspecialty training in Head and Neck Oncologic Surgery,
01
Recent Publications:
Argiris A, Lee SC, Feinstein T, Thomas S, Branstetter BF 4th, Seethala R, Wang L, Gooding W,
Grandis JR, Ferris RL. Serum biomarkers as potential predictors of antitumor activity of
cetuximab-containing therapy for locally advanced head and neck cancer. Oral Oncol. 2011 Aug
31. 1-6
Niemeier LA, Kuffner Akatsu H, Song C, Carty SE, Hodak SP, Yip L, Ferris RL, Tseng GC,
Seethala RR, Lebeau SO, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforov YE. A
combined molecular-pathologic score improves risk stratification of thyroid papillary
microcarcinoma. Cancer. 2011 Aug 31. 1-9
Nikiforov YE, Ohori NP, Hodak SP, Carty SE, Lebeau SO, Ferris RL, Yip L, Seethala RR,
Tublin ME, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforova MN. Impact of Mutational
Testing on the Diagnosis and Management of Patients with Cytologically Indeterminate Thyroid
Page
23Nodules: A Prospective Analysis of 1056 FNA Samples. J Clin Endocrinol Metab. 2011 Aug 31.
1-8
Visus C, Wang YY, Lozano-Leon A, Ferris RL, Silver S, Szczepanski MJ, Brand RE, Ferrone
CR, Whiteside TL, Ferrone S, Deleo A, Wang X. Targeting ALDHbright human carcinoma
initiating cells with ALDH1A1- specific CD8+ T cells. Clin Cancer Res. 2011 Aug 19. 1-32
Lee SC, Srivastava RM, López-Albaitero A, Ferrone S, Ferris RL. Natural killer (NK):dendritic
cell (DC) cross talk induced by therapeutic monoclonal antibody triggers tumor antigen-specific
T cell immunity. Immunol Res. 2011 Aug;50(2-3):248-54.
O’Neill M, Heron DE, Flickinger JC, Smith R, Ferris RL, Gibson M. Posttreatment Quality-of-
Life Assessment in Patients With Head and Neck Cancer Treated With Intensity-modulated
Radiation Therapy. Am J Clin Oncol. 2011 Oct;34(5):478-482.
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24Joseph M. Furman, MD, PhD
Professor, Departments of Otolaryngology, Neurology,
Bioengineering and Physical Therapy
Director, Division of Balance Disorders
UPMC Eye & Ear Institute, Suite 500
200 Lothrop Street
Pittsburgh, PA 15213
Phone: 412 647-2115 Office
Fax: 412 647-2080
Email: furmanjm@upmc.edu
Links
PubMed
NIH RePorter
CV: Joseph M. Furman, MD, PhD
Research Description:
Dr. Furman’s research concerns human vestibular function and balance disorders. On-going
research projects include: the effects of aging on the human balance system, migraine-related
dizziness, balance disorders in patients with anxiety, the development of new tests of vestibular
function including The Gaze Stability Test and Computerized Head Thrust Testing, and the
interaction between cognitive function and balance function. Dr. Furman’s research is performed
in a collaborative environment with physical therapists, bioengineers, neuropsychologists,
psychiatrists, and experts in brain imaging.
There are numerous projects that would be appropriate for resident research rotation. The
specific project would depend on the particular interests of the individual.
Education:
BSE, Electrical Engineering, University of Pennsylvania, 1973
Page
25BA, Natural Sciences, University of Pennsylvania, 1973
MD, University of Pennsylvania, 1977
PhD, Bioengineering, University of Pennsylvania, 1977
Medical Internship, Boston Veterans Administration Hospital, 1979-1980
Residency, Neurology, University of California, Los Angeles, 1980-1982
Neurotology Fellow, Sunnybrook Medical Centre, Toronto, 1983
Neurotology/Research Fellow, University of California, Los Angeles, 1983-1984
Recent Publications:
Durrant J, Jennings JR, Redfern M, Furman JM, Fuhrman SI. Dual-task effects of temporal
processing requirements during vestibulo-ocular stimulation and postural challenge in older
subjects. In press
Alsalaheen AB, Whitney SL, Mucha A, Morris LO, Furman JM, Sparto PJ. A framework for
reporting vestibular rehabilitation exercise prescription and its application in the management of
individuals with dizziness and imbalance after concussion. Journal of Neurologic Physical
Therapy. In press
Cohen, M, Casselbrant M, Mandel E, Sparto PJ; Furman JM. Tympanostomy tube placement
and vestibular function in children. Otolaryngology Head-Neck Surgery. In press
Huppert T, Beluk N, Schmidt B, Furman JM, Sparto PJ. Measurement of brain activation during
an upright stepping reaction task using functional near-infrared spectroscopy (fNIRS). Human
Brain Mapping. In press
Whitney SL, Marchetti GF, Furman JM. Factors associated with balance confidence in older
adults with health conditions affecting the balance and vestibular system. Archives of Physical
Medicine and Rehabilitation. Arch Phys Med Rehabil, 92(11) 1884-1891, 2011; PMID 22032223
Furman JM, Fuhrman, SI, Redfern MS, Jennings JR. Interference between postural control and
spatial vs. non-spatial auditory reaction time tasks in older adults. Gait and Posture. In
submission
Page
26Neeraj J. Gandhi, Ph.D.
Associate Professor
Department of Otolaryngology
Affiliations: Department of Bioengineering
Department of Neuroscience
Center for Neural Basis of Cognition
Eye & Ear Institute
200 Lothrop Street, Suite 108
Pittsburgh, PA 15213
Phone 412.647.3076
Fax 412.647.0108
Email neg8@pitt.edu
Website www.pitt.edu/~neg8
Links
PubMed http://www.ncbi.nlm.nih.gov/pubmed?term=gandhi%20nj
NIH RePorter http://projectreporter.nih.gov/reporter.cfm
CV: Neeraj J. Gandhi, PhD
Research Description:
The nervous system continuously monitors the environment and, when necessary, produces overt
or covert behavior in response to the sensory stimulation. To facilitate orientation towards objects
of interest, the sensory representation of target location is transformed into neural commands that
evoke a complex, coordinated, and accurate movement. One aim of Dr. Gandhi’s research is to
understand the neural implementation of coordinated movements. More specifically, we study the
neural control of coordinated movements of the eyes and head, as well as integration of different
types of eye movements (for example, saccades and smooth pursuit).
Page
27In producing orienting behavior, the efficacy of sensory to motor transformation depends on
cognitive processes. One such mechanism, motor preparation, proposes that neural signals
encoding the metrics of a desired movement develop gradually. A second area of Dr. Gandhi’s
research is geared to test the motor preparation hypothesis and to investigate the extent of its
association with other sensorimotor attributes emphasized by varying task-specific requirements.
These objectives are addressed using both experimental (extracellular recording,
microstimulation, chemical microinjections) and computational tools (lumped and distributed
network models). An understanding of the cognitive and motor processes that produce integrated
orienting behavior has diagnostic value for deficits resulting from disease.
Education:
B.S. (Biomedical Engineering), Boston University, 1992
Ph.D., Graduate Group in Bioengineering, University of California, San Francisco & University
of California, Berkeley, 1997
Postdoctoral Fellow, Division of Neuroscience, Baylor College of Medicine, 1998-2002
Recent Publications:
Gandhi NJ. Interactions between gaze-evoked blinks and gaze shifts in monkeys. Experimental
Brain Research, in press, 2012. [PDF]
Katnani HA and Gandhi NJ. Order of operations for decoding superior colliculus activity for
saccade generation. Journal of Neurophysiology, 106:1250-59, 2011. [PDF]
Gandhi NJ and Katnani HA. Motor functions of the superior colliculus. Annual Review of
Neuroscience, 34:205-31, 2011. [PDF]
Bechara BP and Gandhi NJ. Matching the oculomotor drive during head-restrained and head-
unrestrained gaze shifts in monkey. Journal of Neurophysiology, 104:811-28, 2010. [PDF]
Walton MMG, Bechara BP and Gandhi NJ. Effects of reversible inactivation of superior
colliculus on head movements. Journal of Neurophysiology, 99: 2479-2495, 2008. [PDF]
Page
28Jackie L. Gartner-Schmidt, PhD, CCC-SLP
Associate Professor of Otolaryngology
Associate Director, University of Pittsburgh Voice Center
Director, Speech-Pathology Services, University of Pittsburgh Voice Center
Associate Professor, University of Pittsburgh School of Health and Rehabilitation Sciences,
Department of Communication Science and Disorders
UPMC Mercy Hospital
1400 Locust Street
Bldg. B, Suite 11500
Pittsburgh, PA 15219
Phone 412-232-8970
Fax 412-232-8525
jgs@pitt.edu
Links
PubMed: http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gartner-
Schmidt%20J%22%5BAuthor%5D
NIH Reporter
CV: Jackie L. Gartner-Schmidt, PhD, CCC-SLP
Research Description:
Principal Investigator, Validation of the Cough Severity Index (CSI) and Dyspnea
Severity Index (DSI).
Principal Investigator, Basic Concepts in Voice Therapy
Co-Investigator, Aerodynamic Profiles in Females with Muscle Tension Dysphonia
Co-Investigator, Hybrid Model of Vocal Fold Inflammation and Tissue Mobilization.
Co- Investigator, Metabolic Mechanisms of Vocal Fatigue.
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29Co-Investigator, Prospective study on Prevention and Treatment of Voice Problems in
Teachers.
Co-investigator, Clinical, randomized study on treatment for age-related dysphonia.
Collaboration with Emory Voice Center, Atlanta, GA.
Co-investigator, Preliminary prospective investigation of the utility of nimodipine for
acute vocal fold paralysis
Education
BA Honors, Psychology & Music (Vocal Performance), Queen’s University, Ontario, 1989
MA, Audiology and Speech Sciences, Michigan State University, 1994
Fellowship, Bill Wilkerson Center for Otolaryngology, Hearing and Speech Sciences,
Vanderbilt University, 1995
PhD, Speech-Language Pathology, University of Maryland, 2003
Recent Publications
Gillespie A, Verdolini-Abbott K, Gartner-Schmidt J, Rosen C (2011). Aerodynamic profiles of
females with muscle tension dysphonia (MTD). Journal of Speech, Language and Hearing
Research. In revision.
Arffa RE, Krishna P, Gartner-Schmidt J, Rosen CA. Normative Values for the Voice Handicap
Index-10. J Voice. 2011 Aug 3 [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/21816570
Gartner-Schmidt J, Rosen C. Treatment Success for Age-related Vocal Fold Atrophy.
Laryngoscope 2011 Mar;121(3):585-9. http://www.ncbi.nlm.nih.gov/pubmed/21344441
Carroll T, Gartner-Schmidt J, Statham M, Rosen C. Vocal process granuloma and glottal
insufficiency: An overlooked etiology? Laryngoscope. 2010 Jan;120(1):114-20.
http://www.ncbi.nlm.nih.gov/pubmed/19877195
Rosen CA, Gartner-Schmidt J, Casiano R, et al. Vocal Fold Augmentation with Calcium
Hydroxylapatite (CaHA): Twelve Month Report. Laryngoscope. 2009 May;119(5):1033-41.
http://www.ncbi.nlm.nih.gov/pubmed/19274731
Page
30Grant S. Gillman, M.D., F.R.C.S.
Associate Professor, Department of Otolaryngology
University of Pittsburgh School of Medicine
Director, Division of Facial Plastic and Reconstructive Surgery
UPMC Department of Otolaryngology
UPMC Shadyside
500 Centre Ave, Suite 211
Pittsburgh, PA 15232
Phone: 412-621-0123
Email: gillmangs@upmc.edu
Links
PubMed
NIH RePorter
CV: Grant S. Gillman, M.D., F.R.C.S.
Research Description:
Surgical outcomes in nasal airway surgery
Technical challenges in nasal surgery
The effect of nasal airway obstruction on sleep quality
The impact of nasal surgery on quality of life measures
Education:
Undergraduate - University of Manitoba, Canada, 1982
MD, University of Manitoba, Canada, 1987
Residency, University of Western Ontario, London, Ontario,1996
Fellowship, Sinonasal surgery, University of Pittsburgh, 1997
Fellowship, Facial Plastic & Reconstructive Surgery, University of Miam,i 1998
Page
31Recent Publications:
Conrad K, Torgerson C, Gillman G: Applications of Gore-tex implants in rhinoplasy re-
examined after 17 years. Arch Facial Plast Surg 2008;10(4):224-231.
Yang GC, Chiu RJ, Gillman GS: Questioning the need to use Botox within 4 hours of
reconstitution: A study of fresh vs. 2-week-old botox. Arch Facial Plast Surg 2008;10(4):273-
279.
Lee, AS, Schaitkin BM, Gillman GS: Evaluating the safety of frontal sinus trephination.
Laryngoscope 2010;120:639-642.
Gillman GS: Book review: Rhinoplasty: Craft & Magic, Constantian MB (ed.). St. Louis,
Quality Medical Publishing, 2009. Laryngoscope 2010;120:1489-1490.
Man L, Robison JG, Gillman GS: IgG4-related inflammatory pseudotumor mimicking a
posterior ethmoid and sphenoid mass. Submitted for publication – Annals of Otology, Rhinology
and Laryngology, 2010.
Page
32Jennifer Rubin Grandis, M.D., F.A.C.S.
Vice Chair for Research
UPMC Endowed Chair in Head and Neck Cancer Surgical Research
Department of Otolaryngology
Assistant Vice Chancellor for Research Program Integration in the Health Sciences
Professor of Otolaryngology & Pharmacology
University of Pittsburgh School of Medicine
Program Leader, Head & Neck Cancer Program
University of Pittsburgh Cancer Institute
American Cancer Society Clinical Research Professor
Eye & Ear Institute
200 Lothrop Street, Suite 500
Pittsburgh, PA 15213
Phone 412.647.5280
Fax 412.647.2080
Email jgrandis@pitt.edu
Links
PubMed http://www.ncbi.nlm.nih.gov/pubmed?term=Grandis%20JR
NIH RePorter http://projectreporter.nih.gov/reporter.cfm
CV: Jennifer Rubin Grandis, M.D., F.A.C.S.
Research Description:
Dr. Grandis’ research is dedicated to increasing our understanding of the genetic and epigenetic
alterations in the upper aerodigestive tract mucosa, which result in head and neck squamous cell
carcinoma. The overall goal is to identify biomarkers, which can serve to select patients for
molecular targeted therapy. To date, she has examined the role of the epidermal growth factor
receptor (EGFR) signaling and STAT (signal transducer and activator of transcription) signaling
peptides in head and neck carcinogenesis. Strategies aimed at blocking the ligand or receptor
demonstrated anti-tumor efficacy in preclinical models. Based on these promising results, she
Page
33completed a Phase I clinical trial to investigate the toxicity and biologic effects of EGFR
antisense gene therapy. A Phase II trial will open to accrual in 2012 for patients with locally
advanced head and neck cancer.
Activated STAT3 can be targeted using a variety of approaches that are currently under
investigation in her laboratory. Specifically, a transcription factor decoy targeting STAT3 was
recently evaluated in a Pilot study (Phase 0) in head and neck cancer patients to determine the
biologic effects of blocking STAT3 in human tumors. Studies are underway in collaboration with
the Drug Discovery Institute to identify STAT3-selective inhibitors as cancer treatments.
In addition to the EGFR antisense gene therapy and STAT-mediated signaling pathways, Dr.
Grandis’ laboratory is also investigating the interaction between signaling pathways. Specifically,
she is investigating G-protein-coupled receptors (GPCR) including the gastrin-releasing peptide
(GRP), PGE2, and bradykinin in head and neck carcinogenesis. An ongoing clinical trial is
currently examining the biomarker effects of blocking EGFR and/or Src kinases in head and neck
cancer and a phase II trial is testing the effects of combined inhibition of Src kinases and EGFR
in patients with recurrent or metastatic head and neck cancer. Her group recently completed a
comprehensive assessment of the mutational landscape of head and neck cancers and efforts are
underway to distinguish the driver oncogenes to facilitate the design of more effective therapies.
Projects that would be suitable for a resident research rotation include: 1) defined experiments in
cell lines to test the effects of inhibitors or modulation of specific proteins; 2) animal studies to
examine therapeutic mechanisms of investigational reagents; 3) participation in components of
ongoing or planned clinical studies including patient recruitment, data analysis and manuscript
preparation; or 4) interrogation of our comprehensive head and neck cancer database to address
epidemiologic hypotheses.
Education:
B.A. (Biology and Art History), Swarthmore College, 1982
M.D., University of Pittsburgh School of Medicine, 1987
Internship, Department of Surgery, University of Pittsburgh School of Medicine, 1987-88
Residency, Department of Otolaryngology, University of Pittsburgh School of Medicine, 1988-93
Research Fellow, Department of Medicine, Division of Infections Disease, University of
Pittsburgh School of Medicine, 1991-1992
Recent Publications:
Lai SY, Koppikar P, Thomas SM, Childs E, Egloff AM, Seethala R, Branstetter BF, Gooding
WE, Muthukrishnan A, Mountz JM, Lui VWY, Shin DM, Agarwala SS, Johnson R, Couture LA,
Myers EN, Johnson JT, Mills G, Argiris A, Grandis JR. Intratumoral EGFR antisense DNA
therapy in head and neck cancer: first human application and potential antitumor mechanisms.
Journal of Clinical Oncology, 2009 Mar 10; 27(8):1235-42, Epub 2009 Feb 9. PMID: 19204206.
PMCID: PMC2667824. http://jco.ascopubs.org/content/27/8/1235.long
Leeman-Neill RJ, Seethala RR, Singh SV, Freilino ML, Bednash JS, Thomas SM, Panahandeh
MC, Gooding WE, Joyce SC, Lingen MW, Neill DB, Grandis JR. Inhibition of EGFR-STAT3
signaling with erlotinib prevents carcinogenesis in a chemically-induced mouse model of oral
squamous cell carcinoma. Cancer Prevention Research(Phila), 2011 Feb;4(2):230-7. Epub 2010
Dec 16. PMID: 21163936. PMCID: PMC3076320.
http://cancerpreventionresearch.aacrjournals.org/content/4/2/230.long
Page
34Vaezi A, Wang XZ, Buch S, Gooding W, Wang L, Seethala RR, Weaver DT, D’Andrea AD,
Argiris A, Romkes M, Niedernhofer LJ, Grandis JR. XPF expression correlates with clinical
outcome in squamous cell carcinoma of the head and neck. Clinical Cancer Research. 2011 Aug
15; 17(16): 5513-22. Doi: 10.1158/1078-0432. CCR-11-0086. Epub 2011 Jul 7. PMID:
21737503. PMCID: PMC3156890. http://clincancerres.aacrjournals.org/content/17/16/5513.long
Quesnelle KM, Grandis JR. Dual kinase inhibition of EGFR and HER2 overcomes resistance to
cetuximab in a novel in vivo model of acquired cetuximab resistance. Clinical Cancer Research.
2011 Sep 15; 17(18): 5935-44. Epub 2011 Jul 26. PMID: 21791633. PMC Journal-In Process.
http://clincancerres.aacrjournals.org/content/17/18/5935.long
Stransky N, Egloff AM, Tward A, Kostic A, Cibulskis K, Sivachenko A, Kryukov G, Lawrence
M, Sougnez C, McKenna A, Ramos AH, Stojanov P, Carter SL, Voet D, Cortes M, Auclair D,
Saksena G, Guiducci C, Onofrio R, Parkin M, Romkes M, Weissfeld J, Seethala RR, Wang L,
Winckler W, Ardlie K, Gabriel SB, Myerson M, Lander ES, Getz G, Golub TR, Garraway LA,
Grandis JR. The mutational landscape of head and neck squamous cell carcinoma. Science, 2011
Aug 26;333(6046): 1157-60. Epub 2011 Jul 28. PMID: 21798893. PMC Journal-In Process.
http://www.sciencemag.org/content/333/6046/1157.full
Page
35Patricia A. Hebda, PhD
Professor of Otolaryngology and Pathology
Adjunct Professor of Speech and Communication Disorders
University of Pittsburgh
Director, Otolaryngology Wound Healing Research Program
Children's Hospital of Pittsburgh
Children's Hospital of Pittsburgh of UPMC
4401 Penn Avenue
Rangos Research Center, Room 5120
Pittsburgh, PA 15224
telephone: (412) 692-6217
telefax: (412) 692-5075
email: hebda@pitt.edu
Links
PubMed
NIH RePorter
CV: Patricia A. Hebda, PhD
Research Description:
Dr. Hebda is actively involved in research efforts to improve healing of the skin and mucosa of
the ear, nose and throat. As Director of the ENT Wound Healing Research Program, Dr. Hebda
is working with talented graduate students, residents and postdoctoral fellows and has a close
collaboration with other faculty members, notably Joseph E. Dohar, M.D., a pediatric
otolaryngologist and research partner. The goal of their research team is to establish a
Page
36multifaceted program encompassing preclinical and clinical projects. The fundamental purpose is
to develop new, biologically driven therapeutic modalities to promote and optimize wound
healing and tissue regeneration of the upper aerodigestive system. To achieve this goal they have
ongoing projects based on:
characterization of regenerative, or scarless, fetal wound healing
cell therapy and tissue engineering for laryngotracheal mucosa
animal and tissue culture model systems for airway injury
Another component of their research involves characterization of the fibrotic fibroblast phenotype
as exhibited in connective tissue scars, such as keloids and hypertrophic scars in the skin and
stenoses of the airway. The group is pursuing this study of fibrotic healing with scar formation in
children and adults in contrast to the scarless regenerative healing of fetal connective tissues of
skin and airway mucosa.
The group is also investigating the role of inflammation in the pathogenesis of Otitis media,
focusing on the adverse effects of middle ear fluid evoked by Eustachian tube dysfunction and
resultant negative pressure. Even in the absence of bacterial or viral infection, the fluid produced
in response to negative pressure contains inflammatory mediators that can induce structural
changes over the course of weeks and months.
Education:
B.S. (Biochemistry) Michigan State University
Ph.D. (Biochemistry, carbohydrate metabolism) Ohio State University
Fellowship (Collagen biochemistry) University of California, Los Angeles
Recent Publications:
Sandulache VC, Singh T, Li-Korotky HS, Lo CY, Otteson TD, Barsic M, Dohar JE, Hebda PA.
Prostaglandin E2 is activated by airway injury and regulates fibroblast cytoskeletal dynamics.
Laryngoscope 2009;119:1365-1373. PMCID: PMC3000119
Singh T, Sandulache VC, Otteson TD, Barsic M, Klein EC, Dohar JE, Hebda PA. Subglottic
stenosis (SGS) represents a fibrotic airway mucosal response to injury characterized by altered
mucosal fibroblast activity. Arch Otolaryngol Head Neck Surg. 2009;136:163-170. PMCID:
PMC3000122
Li NYK., Vodovotz Y, Hebda PA, Verdolini K. Biosimulation of inflammation and healing in
surgically injured vocal folds. Ann Otol Rhinol Laryngol. 2010;119:412-423. PMCID:
PMC2910548
Silva, RC, Dohar JE, Hebda PA. (2011) Novel rat model of tympanostomy tube otorrhea. Int J
Ped Otorhinolaryngol In press.
Hebda PA, McLevy J, Li-Korotky HS, Cullen Doyle A, Lo C-Y, Yuksel S, JE Dohar. Monocyte
chemotactic protein-1 contributes to middle ear inflammation in a mouse model of OME induced
Page
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