Frédéric F. Little, M.D.

Faculty and Fellows


Assistant Professor of Medicine
Director, Allergy/Immunology Fellowship Training Program
Medical Director, Pulmonary, Allergy, and Sleep Clinics
Clinical Lead, ICD-10 Implementation, Boston Medical Center

Education and Training:

f-little-md1Undergraduate: Harvard College
Medical School: Tufts University School of Medicine
Internship: University of California, San Francisco
Residency: University of California, San Francisco
Fellowship: Boston University
Other Clinical Fellowship: Boston University (Allergy/Immunology)
Post-Doctoral Research Fellowship: Cardiovascular Research Institute, UCSF

Board Certifications:

  • Internal Medicine
  • Pulmonary Disease
  • Critical Care Medicine
  • Allergy/Immunology

Special Interests:

Research:

  • Pulmonary Immunology
  • Salivary Diagnostics of Lung Disease
  • Point of Care Diagnostics of Allergic Disease

Clinical:

  • Asthma/Allergy
  • Critical Care Medicine
  • Eosinophilic Disorders

Dr. Little is an Assistant Professor in the Department of Medicine. He attends in the Medical Intensive Care Unit and on the Pulmonary Consultation Service at Boston Medical Center . His outpatient activity is concentrated in the Adult Asthma Center and Allergy Clinics.

Dr. Little’s longstanding clinical interests and research efforts are focused on examining the nature of airway inflammation in allergic asthma, and translational approaches to diagnostics of allergic disease.

Prior to coming to Boston University, during a postdoctoral fellowship at the UCSF Cardiovascular Research Institute , he investigated the effect of causing an experimental cold in asthmatic and healthy volunteers, followed by concurrent examination of clinical asthma markers (e.g., spirometry, symptoms) and airway secretions by nasal lavage and sputum induction.

In the laboratory, he is using key cytokine transgenic and knockout mice to investigate antigen-dependent and -independent allergic airway inflammation. Specifically, he is investigating interleukin-16 , a major CD4 ligand, as a paradigm for downregulation of antigen-dependent TH2 inflammation. He applies a well described model of allergic airway inflammation in mice that mimics human asthma to better understand the immunoregulation of the allergic response in the lung.

His translational research continues at Boston University as a principle investigator in a clinic-based study to develop a rapid saliva diagnostics platform for determining the causes of deterioration in asthma control. This study has expanded to both Emergency Room populations at B.U. and cohorts of pediatric asthmatics in collaboration Dr. Elizabeth Matsui, Pediatric Allergy/Immunology at Johns Hopkins. This translational approach has also been used in developing a point of care device to accurately and rapidly quantify allergen-specific IgE using component-resolved diagnostics. This latter effort is in collaboration with Drs. M. Selim Unlü and Carolos Lopez in the Boston University College of Engineering.

He has also participated as a Co-Investigator in immunotherapy trials with the NHLBI-funded Inner City Asthma Consortium, in collaboration with the BUMC site PI, Dr. George O’Connor.

Dr. Little’s educational and administrative responsibilities include directing the Boston University Allergy/Immunology Fellowship Training Program and being the Medical Director of the Pulmonary, Allergy and Sleep Clinics. In a more recent global role at Boston Medical Center, Dr. Little will be serving as the Clinician Lead on implementation of ICD-10 across all specialties.

Laboratory Members:

  • Yurekis Montas, BA Research Coordinator, IgE Diagnostics Project
  • Fengzhi Shao, MSc. Senior Research Technician, Mouse models of allergic airway inflammation

Selected Publications:

  1. Little F.F.*, Delgado DM, Wexler PJ, Oppenheim FG, Mitchell P, Feldman JA, Peng RD, Matsui EM* (*equal contribution). Salivary inflammatory mediator profiling and correlation to clinical disease markers in asthma. PLOS One, 2013 (in press).
  2. Reddy D, and Little F.F. Glucocorticoid-resistant asthma: more than meets the eye. Journal of Asthma Sep 2013 (epub).
  3. Monroe M.R., Daaboul G.G., Tuysuzoglu A., Lopez C.A., Little F.F., Unlü M.S. Single nanoparticle detection for multiplexed protein diagnostics with attomolar sensitivity in serum and unprocessed whole blood. Analytical Chemistry. 85, 3698-706, 2013.
  4. Curiel C., Yamasaki H., Si C.P., Jin X., Richmond J., Tuzova M., Wilson K.C., Sullivan B., Jones D., Ryzhenko N., Little F.F., Kupper T., Center D.M., Cruikshank WW. Loss of nuclear pro-IL-16 facilitates skp2 overexpression and p27 inhibition in cutaneous T-cell lymphoma. Journal of Clinical Investigation 121, 4838-4839, 2011.
  5. Monroe M.R., Reddington A.P., Collins A.D., LaBoda C., Cretich M., Chiari M., Little F.F., Unlü M.S. Multiplexed method to calibrate and quantitate fluorescence signal for allergen-specific IgE. Analytical Chemistry. 83, 9485-91, 2012.
  6. Konter J.M., Parker J.L., Baez E., Li S.Z., Ranscht B., Denzel M., Little F.F., Nakamura K., Ouchi N., Fine A., Walsh K., Summer R.S.. Adiponectin attenuates lipopolysaccharide-induced acute lung injury through suppression of endothelial cell activation. Journal of Immunology 188, 854-863, 2012.
  7. Blicharz TM, Siqueira WL, Helmerhorst EJ, Oppenheim FG, Wexler PJ, Little F.F., Walt DR. Fiber-optic microsphere-based antibody array for the analysis of inflammatory cytokines in saliva. Analytical Chemistry 15:2106-2114, 2009.
  8. Summer R, Little F.F., Ouchi N, Takemura Y, Aprahamian T, Dwyer D, Fitzsimmons K, Suki B, Parameswaran H, Fine A, Walsh K. Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice. American Journal of Physiology: Lung Cellular and Molecular Physiology 94, L1035-42, 2008.
  9. Little, F.F. Treating acute asthma with antibiotics – Not quite yet (Invited Editorial). New England Journal of Medicine 354, 1632-1634, 2006.
  10. Burkart, K.D., Barton, S.J., Holloway, J.W., Yang, I.A., Cakebread, J.A., Cruikshank, W.W., Little, F.F., Jin, X., Farrer, L.A. , Clough, J.B., Keith, T.P., Holgate, S., Center, D.M., and O’Connor, G.T. Association of asthma with a functional promoter polymorphism in the Interleukin-16 gene. Journal of Allergy and Clinical Immunology 117, 86-91, 2006.
  11. Joyce-Brady, M.J., and Little, F.F. Asthma triggered by viral infections: a persistent and troublesome problem. Advance for Managers of Respiratory Care 14, 44-46, 2005.
  12. Little, F.F. and Cruikshank, W.W. Interleukin-16 and peptide derivatives as immunomodulatory therapy in allergic lung disease. Expert Opinion on Biological Therapy 4:837-46, 2004.
  13. Little, F.F. and Center, D.M. Induced sputum analysis for T-helper type 2 cell regulation: closing the loop (Invited Editorial). Chest 123, 1786-1788, 2003.
  14. De Bie, J.J., Jonker, E.H., Henricks, P.A.J., Hoevenaars, J., Little, F.F., Cruikshank, W.W., Nojkamp, F.P., and Van Oosterhout, A.J.M. Exogenous IL-16 inhibits antigen-induced airway hyper-reactivity, eosinophilia, and Th2-type cytokine production in mice. Clinical and Experimental Allergy 32, 1651-1658, 2002.
  15. Little, F.F., Cruikshank, W.W., and Center, D.M. IL-9 stimulates release of chemotactic factors in human bronchial epithelial cells. American Journal of Respiratory Cell and Molecular Biology. 25, 347-352, 2001.
  16. Fleming, H.E. and Little, F.F. (equal contribution, first authors listed alphabetically), Schnurr D., Avila, P.C., Wong, H., Liu, J., Yagi, S., and Boushey, H.A. Rhinovirus-16 induced common colds in healthy and in asthmatic subjects: Similar changes in upper and lower airways. American Journal of Respiratory and Critical Care Medicine 160, 100-8, 1999.

Book Chapters:

  1. Cruikshank W, and Little F.F. lnterleukin-16: the ins and outs of regulating T-cell activation. Critical Reviews in Immunology 28, 467-483, 2008.
  2. Little, F.F., Wilson , K.C., Berman, J.S., and Center, D.M. Lymphocyte- and macrophage-mediated inflammation in the lung. In: Fishman’s Pulmonary Diseases and Disorders, 4 th ed, Fishman A.P. et al, eds. New York : McGraw-Hill, 2008.
  3. Little, F.F. and Hollingsworth, H.M. Anaphylaxis. In: Intensive Care Medicine. Irwin, R.S and Rippe, J.M., eds. Philadelphia : Lippincott Williams & Wilkins, 2006.
  4. Little, F.F., Cruikshank, W.W., Center, D.M. IL-16 and Airway Hyper-Responsiveness in Asthma. In: Biology of Airway Inflammation – Therapeutic Targets, Eissa, N.T., ed. Series: Lung Biology in Health and Disease. New York: Marcel Dekker. Vol 177, 2003.

Selected Reprints:

  1. Treating acute asthma with antibiotics
  2. Interleukin-16 and peptide derivatives as immunomodulatory therapy in allergic lung disease
  3. Induced Sputum Analysis For T Helper Type 2 Cell Regulation
  4. Tumor Necrosis Factor-alpha Induced Synthesis of Interleukin-16 in Airway Epithelial Cells
  5. Exogenous interleukin-16 inhibits antigen-induced airway hyper-reactivity eosinophilia and Th2-type cytokine production in mice
  6. IL-9 Stimulates Release of Chemotactic Factors from Human Bronchial Epithelial Cells
  7. Rhinovirus-16 Colds in Healthy and in Asthmatic Subjects

Clinic Sites:

Adult Asthma Center and Allergy Clinics
Doctor’s Office Building, Boston Medical Center