Professor of Surgery
Professor of Pediatrics (Secondary)
Office Phone: 202-476-4270
- BA, University of Florida, 1985
- MD, Wayne State University, 1991
My interests have always gravitated toward the basic sciences, and so it was no surprise to find myself considering a career as a microbiologist at the University of Florida in Gainesville. Initially, my studies as an undergraduate were interesting, but I always felt that something was missing. It was not until I did some volunteer work assisting residents and nurses in the care of patients and their families at Shands Hospital in Gainesville, Florida, that I realized that this interaction was just as important to me as the actual science. Medicine, which integrated biomedical science with patient care, seemed to be a logical profession to pursue, so I applied to Wayne State Medical School in Detroit and was accepted in 1987.
I thoroughly enjoyed all my medical school classes and rotations, but a one week rotation in pediatric otolaryngology changed everything. I knew that I had found the "perfect fit," and was determined to pursue a career as a pediatric otolaryngologist. I applied to and was accepted into the otolaryngology residency program at the State University of New York (SUNY) in Buffalo, where I had the opportunity to work with Linda Brodsky M.D., an exceptional teacher, both in the clinical and research arenas. Under her direction, and that of Bernice Noble, Ph.D., Department of Microbiology and Pathology, SUNY Buffalo, I began to develop a research focus on the pathophysiology of pediatric chronic rhinosinusitis (CRS).
After completing my otolaryngology residency in Buffalo, I began a two-year pediatric otolaryngology fellowship (1996-1998) at Children’s National in Washington, D.C. This 2 year fellowship was paramount to my career development. At Children’s National, I worked with 3 outstanding pediatric otolaryngologists: George Zalzal M.D., Sukgi Choi, M.D., and Scott Schoem, M.D. They were all superb instructors and taught me the subtleties of managing otolaryngology problems in children. Dr. Zalzal, in particular, was exceptional, not only as a clinical instructor, but as a Division Chief and mentor. He was instrumental in arranging a research block for me during my fellowship, which I carried out in the laboratory of Mary Rose, Ph.D., an international expert on mucin glycoproteins and their roles in mucus overproduction in the lower respiratory tract. Under Dr. Rose’s tutelage, I began to investigate the mucin profile in the sinus tissues of pediatric patients with CRS and was awarded an institutional grant during my fellowship to pursue this project.
I finished my fellowship and was invited to stay on faculty by Dr. Zalzal and became a Pediatric Otolaryngology Attending at Children’s National, Assistant Professor in the Department of Otolaryngology and Pediatrics at the George Washington University, and a junior investigator in the Center for Genetic Medicine, Children’s Research Institute. This was a marvelous opportunity as my ultimate career goal was to work in an academic setting as a physician scientist. In particular, I was able to continue the work I had begun on pediatric CRS as well as teach otolaryngology residents and fellows and hopefully, interest them in pediatric CRS.
As junior faculty, I continued my investigations looking at the mucin profile in the sinus tissues of pediatric patients with CRS. I also continued to add sinus mucosal specimens from normal sinus tissues in addition to sinus tissues from children with CRS and cystic fibrosis to the sinus mucosa tissue bank I created with Dr. Rose, which was not only critical for not only this project, but for subsequent studies exploring the relationship between mucin gene expression and inflammatory mediators. From these early investigations the most compelling data was that the sinus tissues in the diseased patients generally had significant submucosal gland (SMG) hyperplasia/hypertrophy compared to controls, however, the etiology of the SMG hyperplasia remained elusive. I also continued teaching otolaryngology residents from 3 separate residency programs; Georgetown, George Washington and The National Capitol Consortium (Walter Reed/Navy) as well as the Children’s National pediatric otolaryngology fellows.
With the support of Dr. Eric Hoffman, who had become the Director of Genetic Medicine Research at Children’s National, and in collaboration with Dr. Mary Rose, I initiated genome wide expression array analyses on sinus mucosal tissue from children with CRS and non-diseased controls in order to identify genes and pathways implicated in the etiology of glandular hyperplasia in this disease. The microarray analyses yielded very interesting data on the altered expression of inflammatory, innate immune mediators and glandular development genes in the sinus tissues of these patients, and resulted in an R21 award(Peña/Rose, Co-PIs). These gene products were indeed present in the sinus tissues of pediatric CRS patients. However, since we were looking at sinus mucosa at the end stage of disease, we were not any closer to evaluating the relationship between environmental or pathogenic triggers, and the resultant immune/inflammatory mediators and the glandular hyperplasia demonstrated earlier in the sinus tissues of CRS patients. In order to do this, in vitro models representing in vivo sinus mucosa needed to be developed. We received a second R-21 award (Peña/Wu, Co-PIs) to develop these models, and the preliminary data generated to date, is robust and sufficient to support an RO1 application (Peña/Rose, Co-PI), which is in the process of being written.
Currently, I am an Associate Professor in the Department of Otolaryngology and Pediatrics, and Integrative Systems Biology at George Washing University. As a pediatric otolaryngologist, I continue to work to improve the health and lives of children and their families, and teach otolaryngology residents and fellows diagnostic and treatment strategies to manage pediatric ENT disorders. As a physician scientist, I continue to conduct translational research in pediatric chronic rhinosinusitis and serve as a research mentor for both post-doctoral fellows and residents in basic science research projects aimed at better delineating the relationship between inflammation and mucous overproduction in children with pediatric chronic rhinosinusitis.
1. Title: Mucins in Pediatric Sinusitis
Funding Agency: Discovery Fund Award, Children’s Research Institute Research Advisory Council, Children’s National, Washington, D.C. Date: 1997 ($14,975.00)
Role: Principle Investigator
Effort: 30% This grant was used to initiate study of the pathogenesis and pathophysiology of pediatric chronic rhinosinusitis. A sinus tissue bank was created in order to continue further studies.
2. Title: Mucins and Pediatric Sinusitis
American Society of Pediatric Otolaryngology Award
Funding Agency: American Society of Pediatric Otolaryngology
Date: 2000-2001 ($9,754.00)
Role: Principle Investigator
3. Title: The Role of Mucins in Pediatric Sinusitis
Minority Investigator Research Supplement PA-01-079
(Parent Grant: ROI HL 33152; Mary Rose P.I.)
Funding Agency: NIH, NHLBI
Date: 2003 – 2005 ($118,989.00)
2000 – 2002 ($42,576.00)
Role: Principle Investigator
These grants focused on the mucus hypersecretion seen in children with chronic rhinosinusitis and on establishing what secretory cells and/or mucin glycoproteins are overexpressed in pediatric chronic rhinosinusitis.
4. Title: Molecular Profiles and Gene Expression of Nasal Polyps in Cystic Fibrosis
Funding Agency: Cystic Fibrosis Foundation
Date: 2006-2009 ($86,400.00)
Role: Principle Investigator 44
This pilot project analyzed the sinus mucosa mucin expression and gene expression arrays of chronic rhinosinusitis patients with cystic fibrosis.
5. Title: Genetic Approaches to Lung Diseases and Disorders in Washington, D.C.
K12 Career Development Program: HL090020-01 (Eric Hoffman P.I.)
Funding Agency: NIH, NHLBI
Date: 2007-2012 ($1,850,000.00)
Role: Mentor to Diego Preciado, M.D., Ph.D., and Xiaofang Wu, M.D.
This project provided funding to train junior faculty in genomics and genetics of respiratory system diseases.
6. Title: Impact of Inflammatory Genes on Glandular Hyperplasia in Children with Sinusitis Exploratory/Developmental Research Grant Award, 1R21AIO83995-01
Funding Agency: DHHS/NIH/NIIAID/DEA/GMP
Date: 2009 –2012 ($473,000)
Role: Co-Principle Investigator (with Mary Rose, Ph.D.)
This project investigated the role of inflammatory induced submucosal glandular hyperplasia in the pathogenesis of mucus hypersecretion in chronic rhinosinusitis
7. Title: Mucous Obstruction in Upper Respiratory Diseases: Targeting the Mucin Glycoprotein
(Diego Preciado P.I.)
Funding Agency: George Washington University Medical Center Facilitating Funds
Date: 2010 – 2011 ($27,000)
This project studied the quality and quantity of mucins in chronic otitis media and chronic rhinosinusitis.
8. Title: Tobacco Smoke Exposure Effects on Sinonasal Mucosa
Funding Agency: Flight Attendants Medical Research Initiative Clinical Innovator Award
Date: 2011-current ($300,000)
Role: Co-Principle Investigator (with Diego Preciado, M.D., Ph.D.)
Effort: 5% 45
This project investigates the effects of tobacco smoke exposure on mucus over production in sinonasal mucosa with regard to glandular hyperplasia and regulation of mucin gene expression.
9. Title: An in vitro Model of Glandular Hyperplasia in Pediatric Chronic Rhinosinusitis Exploratory/Developmental Research Grant Award, 1R21AI097520-01
Funding Agency: DHHS/NIH/NIIAID/DEA/GMP
Date: 2012 – 2015 ($473,000)
Role: Co-Principle Investigator (with Xiaofang Wu, M.D.)
This project will develop 3-dimenstional models using control and CRS sinus epithelial cells to investigate how inflammation triggers the histological and molecular changes that occur in the sinus mucosa of CRS patients.
10. Title: Omics of Pediatric Lung Disease in Washington, D.C.
K12 Career Development Program: HL119994-01 (Eric Hoffman P.I.)
Funding Agency: NIH, NHLBI
Date: 2013-2018 ($1,850,000.00)
Role: Mentor to Xiaofang Wu, M.D.
This project provides funding to train junior faculty in the proteomics of respiratory system diseases.
11. Title: CXCL5 and POSTN Drive Crosstalk and Glandular Hyperplasia in Pediatric Sinusitis
The Career Development Academic Enrichment Fund (Xiaofang Wu P.I.)
Funding Agency: Children’s Research Institute
Role: Mentor to Xiaofang Wu, M.D.
To provide junior faculty investigators, completing a period of funding either by career development awards or other equivalent institutional or external support, with the opportunity to apply for bridge fund support between current funding and other mechanisms of independent federal (e.g., ROI, R21, UO1, PO1) or peer-reviewed equivalent research funding.
Clinical Medicine Small Group Demonstration Sessions at the State University of New York Buffalo School of Medicine. Instructor for Otolaryngology Section of Physical Examination Course, Buffalo, New York, 1994
Clinical Medicine Small Group Demonstration Sessions at the State University of New York Buffalo School of Medicine. Instructor for Otolaryngology Section of Physical Examination Course, Buffalo, New York, 1995
Teaching and Evaluation Seminar at the State University of New York Buffalo School of Medicine, Buffalo, New York, 1996
Tympanostomy Tube Management, Perry Family Health Center, Washington, D.C., 2000
13th Annual George Washington Pediatric Board Review, Otolaryngology Section, Bethesda, Maryland, 2003
14th Annual George Washington Pediatric Board Review, Otolaryngology Section, Bethesda, Maryland, 2004
University of Medicine and Dentistry of New Jersey Resident Conference. Tracheal Disorders, Newark, New Jersey, 2004
University of Medicine and Dentistry of New Jersey Grand Rounds. Evaluation and Management of Sialorrhea, Newark, New Jersey, 2004
16th Annual George Washington Pediatric Board Review, Otolaryngology Section, Bethesda, Maryland, 2006
George Washington University 4th Year Medical Student Capstone Course, Tracheotomy Management, Washington, D.C., 2009
The Hospital for Sick Children Pediatric Center 2nd Annual Respiratory Symposium, Management of Complications from Chronic Tracheotomy Tubes, Washington, D.C., 2011
The Hospital for Sick Children Pediatric Center 3rd Annual Respiratory Symposium, Management of Complications from Chronic Tracheotomy Tubes, Washington, D.C., 2012
Southern and Central Maryland Pediatric Society. Sore Throats, Ear Aches, and Sleepless Nights, Upper Marlboro, Maryland, 2013
The Hospital for Sick Children Pediatric Center 4th Annual Respiratory Symposium, Speech and Swallowing in Pediatric Tracheotomy Patients, Washington, D.C., 2013
The Hospital for Sick Children Pediatric Center 5th Annual Respiratory Symposium, Pediatric Aerodigestive Tract Anomalies: Implications and Management Strategies, Washington D.C., 2014
Video on Sinonasal Pain for New Release Sinusitis Pain Awareness Month, American Academy of Otolaryngology, Arlington, Virginia, 1999
Cleft Lip and Palate: A Comprehensive Team Approach Seminar. Common ENT Problems in the Cleft Palate Patient. Washington, D.C., 1999
Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee, Food and Drug Administration. Medical and Surgical Management of Drooling, Rockville, Maryland, 2001
Society for Ear, Nose, and Throat Advances in Children. Gaps in Health Care for Children: The Impact of Language and Culture, Gaps Impacting Health Care for Children Panel, Salt Lake City, Utah, 2009
Cherry Blossom Otolaryngology Update at George Washington University Medical Center Medical Center. When to Operate on the Pediatric Runny Nose, Washington, D.C., 2010
Allergy-Immunology Research Conference at Northwestern University’s Feinberg School of Medicine. An In Vitro Model of Glandular Hyperplasia in Pediatric Chronic Rhinosinusitis, Chicago, Illinois, 2011
American Society of Pediatric Otolaryngology Scientific Program, Moderator Section #7 Voice; San Diego, California, 2012
Pediatric Hands-on Airway Endoscopy Course, Children’s National, Simulation lab instructor for bronchoscopy, Washington D.C., 2015
Pediatric Hands-on Airway Endoscopy Course, Children’s National, Cough and Hoarseness Panel; Washington D.C., 2015
16th Annual McGill University Update in Otolaryngology-Head and Neck Surgery Meeting. Emergencies in Pediatric Otolaryngology, Mont Tremblant, Canada, 2012
16th Annual McGill University Update in Otolaryngology –Head and Neck Surgery Meeting. Pediatric Emergency Cases Panel, Mont Tremblant, Canada, 2012
Clinical Programs Developed
Complex Sinusitis Clinic, 2014 –present
This multidisciplinary clinic and program was developed to provide comprehensive evaluations and management strategies for patients with complex sinus disease and concurrent lower respiratory tract pathologies. Treatment options are designed to address the entire airway and can include pharmacologic management and/or surgical intervention. Patient referral base is regional and international.
I have always been interested in the relationship between inflammation and mucous hypersecretion that characterizes many respiratory tract diseases including pediatric chronic rhinosinusitis (CRS). In fact this interest was one, among many reasons, that I pursued a career in otolaryngology. As a resident, I had the good fortune to work with mentors that were investigating the immunocompetence of the sinus mucosa in children with pediatric CRS and began to develop a research focus on the pathophysiology of this disease. Initially, I performed histological and immunohistochemical analyses on pediatric sinus tissues and from these analyses published a study on the local inflammatory and immune cell population in children with CRS (1). Additionally, I assessed the immunocompetence of these cells by their ability to produce IL-1β and TNF - α. I received three Otolaryngology Resident Research Awards (third place: 1994; first place:1995 and 1996) at the State University of New York, Buffalo for this work and presented the data nationally at the American Academy of Otolaryngology-Head and Neck Conferences in San Francisco, California (1995) and in New Orleans, Louisiana (1996).
Although interesting, the data did not provide any earth shattering information. I then began fellowship training in Pediatric Otolaryngology and was introduced to Mary Rose, Ph.D., an international expert on mucin glycoproteins and their roles in mucus overproduction in the lower respiratory tract. Since hypersecretion of mucins is a characteristic presentation in pediatric CRS, Dr. Rose was the ideal research mentor for me. Under her tutelage, I began to investigate the mucin profile in the sinus tissues of pediatric patients with CRS and was awarded an institutional grant during my fellowship to pursue this project. In order to do this, I started collecting specimens from normal sinus mucosa in addition to sinus tissues from children with CRS and cystic fibrosis. I realized that creating a sinus mucosa tissue bank was a critical step not only for this project, but for subsequent studies exploring the relationship between mucin gene expression and inflammatory mediators.
I was then invited to join the Otolaryngology faculty at Children’s National Medical Center. This was a great opportunity as I could continue to work with Dr. Rose on what was at this point, our mutual interest in the pathophysiology of pediatric CRS. As junior faculty, I performed histological and histochemical analyses on the morphology of sinus mucosa and showed the absence of goblet cell hyperplasia (2) and the presence of submucosal gland hyperplasia (3) in CRS patients. Additionally, I performed immunohistochemical analyses of MUC5AC, MUC5B, and MUC7 mucin expression in the sinus mucosa of children with and without CRS and observed an increase only in MUC5B expression, which reflected the submucosal gland hyperplasia and/or hypertrophy in children with CRS. This work resulted in two publications in peer review journals (2, 3) in addition to several oral and poster presentation at scientific meetings. Of all the data collected, the most compelling was that the sinus tissues in the diseased patients generally had significant submucosal gland (SMG) hyperplasia/hypertrophy compared to controls. This then led me to question why the glands were so hyperplastic-could it be that inflammatory mediators were triggering this hyperplasia/hypertrophy generating the rhinorrhea that is so often seen in children with CRS?
At about this time, Eric Hoffman, Ph.D., became Director of the Center of Genetic Medicine Research at CNMC and I became exposed to microarray analysis. Through extensive discussions with both Drs. Rose and Hoffman, I came to understand the power of this technique and realized it would allow me to evaluate the differential expression of inflammatory/immune genes in CRS and control sinus tissues and ultimately lead to identification of genes and pathways involved in submucosal gland formation and hyperplasia. In collaboration with Dr. Mary Rose and Dr. Xiaofang Wu, a post-doctoral student who had recently joined Dr. Rose’s lab, I initiated genome wide expression array analyses on sinus mucosal tissue from children with or without CRS in order to identify genes and pathways implicated in the etiology of glandular hyperplasia in pediatric patients with CRS. Specific inflammatory genes in the adaptive and innate immune system were upregulated in the array analyses and validated by RT-PCR in an independent set of sinus mucosa tissues. Two of these inflammatory genes (CXCL5 and CXCL13) were novel to the CRS field. This data was presented at the American Society of Pediatric Otolaryngology Conference and published in a special pediatric issue of Archives of Otolaryngology (4).
The microarray analyses yielded very interesting data on the altered expression of inflammatory, innate immune mediators (5) and glandular development genes (6) in the sinus tissues of children in the diseased and control cohorts and resulted in an R21 award(Peña/Rose, Co-PIs). While these gene products could be found in the sinus tissues of pediatric CRS patients, I realized that in order to evaluate the relationship between environmental or pathogenic triggers, and the resultant immune/inflammatory mediators and the glandular hyperplasia demonstrated earlier in the sinus tissues of CRS patients, an in vitro model representing in vivo sinus mucosa needed to be developed. Drs. Rose, Wu and I began to address this under the auspices of a second R21 award (Peña/Wu, Co-PI) by developing a 3 dimensional (3D) model wherein human bronchial epithelial (HBE) and nasal epithelial (HNE) cells grown on the extracellular matrix Matrigel differentiate into glandular acini (7). Furthermore, our preliminary data with inflammatory mediators and growth factors demonstrated a response in our acini HNE model indicating that HNE cells contain pluripotent cells capable of responding to environmental agents and bacterial byproducts. HNE cells grown in collagen 1 (COL1) gels differentiate into tubules which are absent in Matrigel, whereas HNE cells co-cultured with fibroblasts differentiate into a model that is morphologically similar to in vivo epithelium (8). As result, it has become clear that we not only need to develop a model that is morphologically similar to in vivo epithelium, but rather, we need to develop models that can also permit investigation into the 2 major clinical presentations of CRS, defined by the presence or absence of nasal polyps which are hyperplastic sinus mucosa that often extend into the nasal cavity.
Ultimately, these models will revolutionize the understanding of pediatric CRS as they will provide researchers a means by which to study the histologic and molecular changes of the pediatric sinus mucosa in real time and sequentially follow the evolution of the disease in relevant clinical presentations. With the support of the R21s awards, substantial preliminary data has been generated to write an RO1 application (currently in progress) to continue pursue our understanding of the pathogenesis of pediatric sinusitis.Reference:
1. Peña M, Brodsky L, Noble B. Immunohistochemical analysis of mononuclear inflammatory cells in nasal and sinus epithelium in children with sinusitis. Amer J Rhinol, 1996; 10(3); 149-159. PMID: 101490775
2. Peña M, Aujla P, Patel K, Zalzal G, Rose M. Immunohistochemical analyses of MUC5AC mucin expression in sinus mucosa of children with sinusitis and controls. Ann Otol Rhinol Laryngol, 2005; 114(12); 958-965. 16425564
3. Peña M, Aujla P, Patel K, Zalzal G, Rose M. Immunohistochemical analyses of MUC5AC mucin expression in sinus mucosa of children with sinusitis and controls. Ann Otol Rhinol Laryngol, 2005; 114(12); 958-965. 16425564
4. Wu X, Ghimbovschi S, Aujla P, Rose M, Peña M. Expression profiling of inflammatory mediators in pediatric sinus mucosa. Arch Otolaryngol Head Neck Surg, Jan 2009:135(1):65-72. PMID: 19153309
5. Wu X, Mimms R, Lima R, Peters-Hall J, Rose M, Peña M. Localization of inflammatory mediators in pediatric sinus mucosa. Arch Otolaryngol Head Neck Surg, 2012; 138(4); 389-397. PMID: 22508623
6. Wu X, Peters-Hall J, Ghimbovschi S, Mimms R, Rose M, Peña M. Glandular gene expression of sinus mucosa in chronic rhinosinusitis with and without cystic fibrosis. Am J Respir Cell Mol Biol, 2011; 45(3); 525-33. PMID: 21177983
7. Wu X, Peters-Hall J, Bose S, Peña M, Rose M. Human bronchial epithelial cells differentiate to 3D glandular acini on basement membrane matrix. Am J Resp Cell Mol Biol, 2011 Jun; 44(6); 914-21. PMID: 20724555
8. Wu X, Mimms R, Banigan M, Lee M, Elkis V, Peters-Hall J, Mubeen H, Joselow A, Peña M, Rose MC. Development of Glandular Models from Human Nasal Progenitor Cells. Am J Respir Cell Mol Biol, Nov, 2014. PMID: 25412193
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Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.