Our Providers

David Paik, MD
  • Assistant Professor of Ophthalmic Science (in Ophthalmology)
David Paik, <span>MD</span>

Collagenous tissue cross-linking is a vast and varied field indeed. The Paik Laboratory for Tissue Cross-linking at Columbia University Medical Center is interested in many aspects of collagenous tissue cross-linking, including

  1. inducing tissue cross-linking as a therapy for improving mechanical tissue strength in patients (i.e. keratoconus, post-LASIK keratectasia, progressive myopia);
  2. modulating cross-linking in healing wounds as a means to prevent negative sequelae from scarring and
  3. understanding the role that differences in both enzymatic and non-enzymatic connective tissue protein (i.e. collagen and elastin) cross-linking may have in contributing to the development of human disease (keratoconus, myopia, aging, age-related disease).

Dr. Paik’s laboratory uses a variety of analytical techniques related to the topic of cross-linking, including chemical, biochemical, thermodynamic, biomechanical, and histologic, maintaining close collaborations with chemists, clinicians, cell biologists, and biomechanical engineers. Some of the analytical methods that we use include: high pressure liquid chromatography (HPLC) with diode array (DAD), fluorescence (FLD), and mass (MSD) detectors, thermodynamic analyses using thermal shrinkage temperature (Ts) and differential scanning calorimetry (DSC), soft tissue mechanical testing, histologic methods, and various forms of live animal imaging.

From a therapeutic standpoint, the ability to selectively enhance the biomechanical properties of a given tissue in vivo while preserving native tissue architecture and cellular functionality (i.e. cross-linking) has numerous potential human clinical applications. Because the tensile strength of a tissue is determined largely by its connective tissue protein structure and integrity, the proteins that make up such a structure (i.e. fibrillar collagens) provide a key target for enhancing overall tissue strength. A key prototype of therapeutic cross-linking is in the treatment of corneal disease. Indeed, in vivo tissue cross-linking using riboflavin photochemistry has recently been shown to be an effective means to halt the progression of cornea destabilization seen in keratoconus and post-LASIK keratectasias. This novel treatment is now being used throughout the world and is gaining widespread acceptance. However, several drawbacks have been noted using the current method and a better method may be available. In this regard, the laboratory is developing a technique to induce cross-linking using aliphatic β-nitroalcohols in a topical form as an alternative approach to the riboflavin photochemical method and is actively engaged in pre-clinical studies under a federally funded project (R01 EY020495-01A1).

Staff
Quan Wen, MD – Associate Research Scientist
MiJung Kim, PhD – Associate Research Scientist
Anna Takaoka, PhD – Postdoctoral Research Fellow
Xia Li, PhD – Staff Associate
TBA - Laboratory Assistant

Lab Locations

  • Edward S. Harkness Eye Institute Research Annex

    160 Fort Washington Avenue
    Eye Research Annex Room 715
    New York, NY 10032
    Phone:
    (212) 342-5455
    Email:
    dcp14@columbia.edu

Honors & Awards

Selected Awards and Honors

  • 2010 - Present American Board of Surgery Certification in Surgical Critical Care (certificate #002761)
  • 2006 - Present American Board of Surgery Certification in Surgery (certificate #51485)
  • 2003 - Present National Scientific Advisory Council member American Federation for Aging Research (AFAR)
  • 2008 - 2009 Recipient Columbia University 2008 Irving Institute for Clinical and Translational Research Pilot Study Award
  • 2000 - 2004 Recipient, Mentored Clinical Scientist Development Award (K08) National Institute on Aging
  • 1999 - 2001 Recipient, American Federation for Aging Research (AFAR) Research Grant
  • 1992 Diplomat of the National Board of Medical Examiners

Research Interests

  • Therapeutic corneal collagenous tissue cross-linking – Together with Dr. Stephen Trokel, Dr. Paik’s laboratory is developing a novel treatment for diseases involving corneal destabilization such as keratoconus and post-LASIK keratectasias using chemical cross-linking technology.
  • Therapeutic scleral collagenous tissue cross-linking– Together with Dr. Donny Hoang, Dr. Paik’s laboratory is developing a novel treatment for diseases involving scleral destabilization such as progressive myopia and staphaloma using chemical cross-linking technology.
  • Chemical mechanism determination and stability studies for nitroalcohols – In collaboration with the Turro Chemistry Laboratory at Columbia University, Dr. Paik’s laboratory is pursuing mechanistic, catalytic, and stability studies involving aliphatic β-nitroalcohols.
  • Modulation of collagen cross-linking in healing wounds as a method to alter the material properties of forming scar tissue – Dr. Paik’s laboratory is evaluating the therapeutic use of collagen enzymatic cross-linking modulation for improvement of intraocular pressure control after glaucoma implant surgery (a wound healing study).
  • Native collagen cross-link analysis in corneal and scleral destabilization – Dr. Paik’s laboratory is studying the relationship between native collagen cross-linking and tissue mechanical destabilization in diseases such as keratoconus.

NIH Grants

  • THERAPEUTIC CORNEAL CROSS-LINKING USING FORMALDEHYDE RELEASING AGENTS (Federal Gov)

    Apr 1 2010 - Feb 29 2020

    A NOVEL TREATMENT FOR KERATOCONUS AND KERATECTASIAS USING NI TRO TECHNOLOGY (Federal Gov)

    Jan 1 2009 - Jun 30 2011

Publications

Publications relevant to current projects

Wen Q, Kim MJ, Hoang QV, Trokel SL Paik DC. Aliphatic β-nitroalcohols for therapeutic corneoscleral cross-linking: catalytic studies. In preparation.

Kim MJ, Wen Q, Hoang QV, Trokel SL, Paik DC. Topical alternatives to therapeutic riboflavin photochemical tissue cross-linking: a comparison of cell toxicity thresholds. In preparation.

Li X, Li Y, Trokel SL, Turro NJ, Paik DC. Aliphatic β-nitroalcohols for therapeutic corneoscleral cross-linking: chemical stability studies using 1H-NMR. submitted.

Li X, Li Y, Paik DC, Turro NJ. Mechanistic and Catalytic Studies of β-Nitroalcohol Cross-linking with Polyamine. Journal of Applied Polymer Science. 2012; Oct 8, 2012; DOI: 10.1002/app.38604.

Chandran PL, Paik DC, Holmes JW. Structural mechanism for alteration of collagen gel mechanics by glutaraldehyde crosslinking. Connect Tis Res. 2012;53(4):285-97.

Wen Q, Trokel SL, Kim MJ, Paik DC. Aliphatic β-nitroalcohols for therapeutic corneoscleral cross-linking: corneal permeability considerations. Cornea. 2012; doi: 10.1097/ICO.0b013e31825646de.

Wen Q, Paik DC. A simple method for measuring aliphatic beta-nitroalcohols using the Griess nitrite colorimetric assay. Experimental Eye Research. 2012;98:52-57.

Paik DC. Aliphatic B-nitroalcohols for corneoscleral cross-linking. J Emmetropia. 2010;1: 92-104.

Solomon MR, O’Connor NA, Paik DC, Turro NJ. Nitroalcohol induced hydrogel formation in amine-functionalized polymers. Journal of Applied Polymer Science. 2010;117:1193-1196.

Paik DC, Solomon MR, Wen Q, Turro NJ, Trokel SL. Aliphatic β-nitroalcohols for therapeutic corneoscleral cross-linking: chemical mechanisms and higher order nitroalcohols. Invest Ophthalmol Vis Sci., 2010;51:836-843.

Paik DC, Wen Q, Airiani S, Braunstein RE, Trokel SL. Initial studies using aliphatic β-nitro alcohols for therapeutic corneal cross-linking. Invest. Ophthalmol. Vis. Sci., 2009;50:1098–1105 DOI:10.1167/iovs.08-2202.

Paik DC, Wen Q, Braunstein RE, Trokel SL. Short chain aliphatic β-nitro alcohols for corneoscleral cross-linking: corneal endothelial cell toxicity study. J Refract Surg. 2008;24(7):S741-7.

Paik DC, Wen Q, Airiani S, Braunstein RE, Trokel SL. Aliphatic β-nitro alcohols for non-enzymatic collagen cross-linking of scleral tissue. Exp Eye Res. 2008;87:279-85.

Paik DC, Saito LY, Sugirtharaj DD, Holmes JW. Nitrite induced cross-linking alters remodeling and mechanical properties of collagenous engineered tissues. Connect Tis Res. 2006;47:163-76.

Additional publications

Paik DC, Larson JD, Johnson SA, Sahm K, Shweiki E, Fulda GJ. Phlegmonous Gastritis and Group A Streptococcal Toxic Shock Syndrome in a Patient Following Functional Endoscopic Sinus Surgery. Surgical Infections. 2010;11(6):45-54.

Jiang R, Barr RG, Camargo CA, Willett WC, Varraso R, Paik DC. Reply to CK Chow (letter to the editor). Am J Clin Nutr. 2008;88:1704.

Jiang R, Camargo CA, Varraso R, Paik DC, Willett WC, Barr RG. Consumption of cured meats and prospective risk of chronic oB.S.tructive pulmonary disease in women. Am J Clin Nutr. 2008;87:1002-8.

Rousseva LA, Gaillard ER, Paik DC, Merriam JC, Ryzhov V, Garland DL, Dillon JP. Oxindolealanine in age-related human cataracts. Exp Eye Res. 2007;85:861-8.

Sun K, Cai H, Tezel TH, Paik DC, Gaillard ER, Del Priore LV. Bruch’s membrane aging decreases phagocytosis of outer segments by retinal pigment epithelium. Mol Vis. 2007;13:2310-19.

Paik DC. Does cured meat consumption damage lung tissue? Respir Med: COPD Update (comment). 2007;3:158.

Jiang R, Paik DC, Hankinson JL, Barr RG. Cured Meat Consumption, Lung Function and Chronic OB.S.tructive Pulmonary Disease Among US Adults. Am J Respir Crit Care Med. 2007;175:798-804.

Paik WK, Paik DC, Kim S. Historical review: the field of protein methylation. Trends Biochem Sci. 2007;32(3):146-52.

Wang Z, Paik DC, Dillon JP, Gaillard ER. Tyrosine nitration site specificity identified by LC/MS in nitrite modified collagen type IV: Implications to retinal pigment epithelial cell dysfunction. Exp Mol Med. 2007;39(1):74-83.

Paik WK, Paik DC, Kim S. Historical review: the field of protein methylation. Trends Biochem Sci. 2007;32(3):146-52.

Jiang R, Paik DC, Hankinson J, Barr RG. Consumption of cured meats, lung function and risk of COPD among US adults. Eur Respir J. 2006;20(Suppl. 50).

Paik DC, Wendel TD, Freeman HP. Cured meat consumption and hypertension: an analysis from NHANES III (1988-94). Nutr Res. 2005;25:1049-60.

Wang Z, Paik DC, Del Priore LV, Gaillard ER. Nitrite-modified extracellular matrix proteins deleteriously affects retinal pigment epithelial cell function and viability: a comparison study with non-enzymatic glycation mechanisms. Cur Eye Res. 2005;30:691-702.

Paik DC, Fu C Bhattacharya J, Tilson M.D.. Ongoing angiogenesis in blood vessels of the abdominal aortic aneurysm. Exp Mol Med. 2004;36(6):524-33.

Paik DC, Saborio DV, Oropeza R, Freeman HP. The epidemiological enigma of gastric cancer rates in the US: was grandmother’s sausage the cause? Int J Epi. 2001;30;181-2.

Paik DC, Dillon J, Galicia E, Tilson M.D.. The nitrite/collagen reaction: non-enzymatic nitration as a model system for age-related damage. Connect Tis Res. 2001;42(2):111-122.

Paik DC, Dillon JP. The nitrite/alpha crystallin reaction: a possible mechanism in lens matrix damage. Exp Eye Res. 2000;70:73-80.

Dillon J, Skonieczna M, Mandal K, Paik DC. The photochemical attachment of the o-glucoside of 3-hydroxykynurenine to alpha-crystallin: a model for lenticular aging. Photochem Photobiol. 1999;69(2):248-53.

Paik DC, Ramey WG, Dillon J, Tilson M.D.. The nitrite/elastin reaction: implications for in vivo degenerative effects. Connect Tis Res. 1997;36(3):241-251.

Peer Reviewer for: Investigative Ophthalmology and Visual Science (IOVS), Experimental Eye Research (EER), Journal of Cataract and Refractive Surgery, Current Eye Research, Journal of Refractive Surgery, Ophthalmic Research, The Ocular Surface, Toxicology