Scott Donaldson

  Donaldson                                                                                     

Degrees

BS:
(1986) U. of Michigan, Ann Arbor, MI

MD:
(1990) U. of Michigan, Ann Arbor, MI

Residency:
(1990-93) Dartmouth, Hanover, NH

Fellowship:
(1993-98) UNC, Chapel Hill, NC

Academic Title:
Associate Professor of Medicine

Office:   6007-A Thurston-Bowles
Phone:   919-966-9198
Fax:       919-966-5178
Email:  scott_donaldson@med.unc.edu

Research Interests:

The lung is protected against inhaled organisms and particles by mucociliary clearance.  Inhaled particles bind to a secreted mucus layer, which rests on top of a thin film of fluid.  The volume/height of this thin fluid layer is tightly regulated so that coordinated ciliary beating efficiently propels this mucus blanket toward the proximal airways.  A key determinant of airway surface liquid volume is the rate of sodium absorption through the epithelial sodium channel (ENaC).  In cystic fibrosis (CF) sodium absorption is excessive, leading to a depleted airway surface liquid layer, poor mucociliary clearance, and subsequent chronic infection.  Research in this lab is directed at understanding the processes that regulate ion transport and mucociliary clearance, in an attempt to develop therapies aimed at correcting the underlying defects in CF lung disease.

One focus of this lab is the regulation of the ENaC, which forms the rate-limiting step in fluid absorption from the lung. Using the xenopus oocyte expression system, the impact of genes encoding candidate proteins on whole cell ENaC currents and single channel kinetics are tested. These results are then used to guide experiments using various epithelial cell models. Ultimately, the goal of this research is to modify ion transport in vivo in a way that improves mucociliary clearance.

A second avenue being explored as a means to alter ion transport in vivo, and thereby enhance mucociliary clearance, is the use of nucleotide receptor agonists. Activation of the dominant airway nucleotide receptor, P2Y2, leads to secretion of chloride/water via non-CFTR chloride channels, mucin secretion via goblet cells, and more rapid ciliary beating. This triad of effects combines to increase mucociliary clearance in normal subjects, as well as in patients with CF. A potential shortcoming of this therapy is the presence of enzymes that hydrolyze typical P2Y2 agonists (e.g. ATP, UTP), thus dramatically decreasing their half-life. Our lab, therefore, is characterizing cell surface and secreted enzymes that may impact the profile of endogenous/exogenous nucleotides in airways, so that therapeutic rational approaches aimed at targeting these receptors may be devised.

donaldson_1

Recent Publications:

Book Chapters

  1. Donaldson SH and Galietta L: New Pulmonary Therapies Directed at Targets other than CFTR, in Riordan J Boucher R, Quinton P (eds): "Cystic Fibrosis: Molecular Basis, Physiological Changes, and Therapeutic strategies”.  Cold Spring Harbor Press; 2013.
  2. Donaldson SH. Aclaramiento Mucociliar Defectuoso en la Fibrosis Quística (“Defective Mucociliary Clearance in Cystic Fibrosis”), in Salcedo Posadas A, Gartner S, Giron Moreno RM, GarciaNovo MD (eds): Tratado de Fibrosis Quística. Aval Cientifico; 2012, 73-80.
  3. Volsko TA, O’Malley C, Donaldson SH, Yankaskas JR and Rubin BK.  Cystic Fibrosis, in Hess, MacIntyre, Mishoe, Galvin and Adams (eds): “Respiratory Care, Principals and Practice, Second Edition”.  Sudbury, MA, Jones and Bartlett Learning, LLC; 2012:826-44.
  4. Brown AW and Donaldson SH: Mucus Abnormalities and Ciliary Dysfunction, in Allen J, Rubenstein R and Panitch H (eds): Cystic Fibrosis.  New York, NY, Informa Healthcare; 2010:24-35.
  5. Donaldson SH, Wolfgang MC, Gilligan PH and Boucher RC: Cystic Fibrosis, in Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th Edition.  Churchill Livingstone Publishers; 2009: 947-955.
  6. Donaldson SH and Boucher RC: Microbiology and Infection in Cystic Fibrosis, in Fishman’s Pulmonary Diseases and Disorders, 4th Edition.  McGraw Hill Publishers; 2008:2173-2182.
  7. Donaldson SH and Boucher RC: Cystic Fibrosis, in Runge M and Patterson C (eds): Principles of Molecular Medicine, 2nd Edition.  Totowa, NJ, Humana Press; 2006:251-258.
  8. Donaldson SH, Yankaskas J: Cystic Fibrosis, in Hess D, MacIntyre N, Mishoe SC, Galvin WF, Saposnick AB, Adams A (eds): Respiratory Care: Principles and Practice.  Orlando, FL, W.B. Saunders Company; 2002:1003-1021.
  9. Donaldson SH, Boucher RC:  Therapeutic Applications for Nucleotides in Lung Disease, in Turner J, Weisman G, and Fedan J (eds):  The P2 Nucleotide Receptors.  Totowa, NJ, The Humana Press Inc.; 1998:413-424.
  10. Erickson RP, Bevilacqua A, Ross C, Donaldson S, Stalvey JRD:  Do BKM sequences play a role in human sex determination? In Haseltine FP, McClure ME, and Goldberg EH (eds):  Genetic Markers of Sex Differentiation.  New York, NY, Plenum Publishing Corporation; 1987:149-159.

Refereed Papers

  1. Donaldson SH and Galietta L: New Pulmonary Therapies Directed at Targets other than CFTR, in Riordan J Boucher R, Quinton P (eds): "Cystic Fibrosis: Molecular Basis, Physiological Changes, and Therapeutic strategies”.  Cold Spring Harbor Press; 2013.
  2. Donaldson SH. Aclaramiento Mucociliar Defectuoso en la Fibrosis Quística (“Defective Mucociliary Clearance in Cystic Fibrosis”), in Salcedo Posadas A, Gartner S, Giron Moreno RM, GarciaNovo MD (eds): Tratado de Fibrosis Quística. Aval Cientifico; 2012, 73-80.
  3. Volsko TA, O’Malley C, Donaldson SH, Yankaskas JR and Rubin BK.  Cystic Fibrosis, in Hess, MacIntyre, Mishoe, Galvin and Adams (eds): “Respiratory Care, Principals and Practice, Second Edition”.  Sudbury, MA, Jones and Bartlett Learning, LLC; 2012:826-44.
  4. Brown AW and Donaldson SH: Mucus Abnormalities and Ciliary Dysfunction, in Allen J, Rubenstein R and Panitch H (eds): Cystic Fibrosis.  New York, NY, Informa Healthcare; 2010:24-35.
  5. Donaldson SH, Wolfgang MC, Gilligan PH and Boucher RC: Cystic Fibrosis, in Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th Edition.  Churchill Livingstone Publishers; 2009: 947-955.
  6. Donaldson SH and Boucher RC: Microbiology and Infection in Cystic Fibrosis, in Fishman’s Pulmonary Diseases and Disorders, 4th Edition.  McGraw Hill Publishers; 2008:2173-2182.
  7. Donaldson SH and Boucher RC: Cystic Fibrosis, in Runge M and Patterson C (eds): Principles of Molecular Medicine, 2nd Edition.  Totowa, NJ, Humana Press; 2006:251-258.
  8. Donaldson SH, Yankaskas J: Cystic Fibrosis, in Hess D, MacIntyre N, Mishoe SC, Galvin WF, Saposnick AB, Adams A (eds): Respiratory Care: Principles and Practice.  Orlando, FL, W.B. Saunders Company; 2002:1003-1021.
  9. Donaldson SH, Boucher RC:  Therapeutic Applications for Nucleotides in Lung Disease, in Turner J, Weisman G, and Fedan J (eds):  The P2 Nucleotide Receptors.  Totowa, NJ, The Humana Press Inc.; 1998:413-424.
  10. Erickson RP, Bevilacqua A, Ross C, Donaldson S, Stalvey JRD:  Do BKM sequences play a role in human sex determination? In Haseltine FP, McClure ME, and Goldberg EH (eds):  Genetic Markers of Sex Differentiation.  New York, NY, Plenum Publishing Corporation; 1987:149-159.