Elliot L. Chaikof, MD, PhD

Johnson and Johnson Professor of Surgery, Harvard Medical School 


 

Chair, Department of Surgery, BIDMC
Surgeon-in-Chief, BIDMC

Harvard Stem Cell Institute
Wyss Institute for Biologically Inspired Engineering

Research Group

Jiaxuan Chen, PhD
Erbin Dai, MD
Carolyn A. Haller, PhD
Oki Ham, PhD
Liying Liu, MD
Appi Reddy Mandhapati, PhD
David Miranda Nieves
Simon Park, PhD
Diane (Dayoung) Park, PhD
Walter Wever, PhD
Daniel Wong, MD

Research Focus

Our laboratory (chaikoflab.org) is focused on the discovery of new drugs and the development of tissue engineered organs based upon the principles of chemistry, biomolecular engineering, and 3-D fabrication technologies. Ongoing research is directed at the following areas.

Drug discovery

Identification of new drugs to inhibit inflammation and thrombosis
Selectins play an important role in the recruitment of leukocytes to inflamed tissue. We are currently synthesizing compounds to block inflammatory responses that contribute to deep venous thrombosis, atherosclerosis, metabolic syndrome, inflammatory bowel disease, and cancer metastasis.

Biomaterials science

Design of anti-thrombogenic surfaces
The development of artificial organs remains limited by the propensity of all synthetic surfaces to induce thrombus formation despite systemic anticoagulation. Current studies are designing surfaces that present molecules that resist clotting and whose bioactive surfaces can be ‘regenerated’ in situ to extend and improve the clinical performance of blood contacting devices, such as vascular grafts, heart valves, left ventricular devices, and implantable artificial lungs and kidneys.

Tissue engineering and regenerative medicine

Engineering blood vessels
Synthetic blood vessel substitutes for cardiac or vascular surgery do not exist. Ongoing efforts in our group seek to design new synthetic collagen and elastin analogues and to assemble them along with vascular wall cells derived from stem cells to engineer a living artery.

Vascular biology

Targeted therapies to promote vascular wall healing
Restenosis remains a major cause of failure after angioplasty and stenting for treatment of lower extremity peripheral arterial disease. New approaches are being developed that target thrombotic and inflammatory events at the site of vessel wall injury through antibody directed targeting of activated platelets.

Accomplishments 2016-2017

Through established collaborations with David Liu, PhD (Chemistry, Harvard University/Broad Institute), and Jian Liu, PhD (Chemistry, University of North Carolina), we have expanded our efforts directed at identifying and harnessing biologically inspired designs to limit blood clotting on artificial surfaces. Additional collaborations have supported ongoing drug discovery efforts including those with Richard Cummings, PhD, Vice Chair of Translational Research in the Department of Surgery and Director, Harvard Medical School (HMS) Center for Glycoscience, and Robert Woods, PhD, Professor of Computational Chemistry, Complex Carbohydrate Research Center, University of Georgia, as well as with Lijun Sun, PhD, Associate Professor of Surgery at HMS and Director of the Center for Drug Discovery in the Department of Surgery. Tissue engineering programs represent collaborations with Chad Cowan, PhD in Cardiology, BIDMC, Axel Guenther, PhD, Professor of Mechanical Engineering at the University of Toronto, and Jennifer Lewis, PhD, Professor of Biologically Inspired Engineering in the Harvard School of Engineering. The development of a new generation of infection-resistant biomaterials represents a collaboration with Joanna Aizenberg, PhD, Professor of Materials Science in the Harvard School of Engineering.

Elected Vice-Chair for Section 01 in the National Academy of Medicine (Physical Sciences, Mathematical Sciences, Computer/Information Sciences, Biomedical Engineering, Engineering Sciences)

Co-Chair, Mapping the Human Glycome in Health and Disease, Radcliffe Institute for Advanced Studies

Member, Convening on the Physician Scientist Workforce, National Institutes of Health

Teaching, Training, and Education

Harvard-MIT HST PhD candidate David Miranda Nieves received a National Defense Science and Engineering Graduate Fellowship to support his PhD studies

Postdoctoral fellow Perla Ayala, PhD, was appointed Assistant Professor, Department Bioengineering, California State University - Long Beach

Postdoctoral fellow E. Vickie Dydek, PhD, joined the scientific staff of MIT Lincoln Laboratory

Postdoctoral fellow Jennifer Gagner, Ph.D., joined the scientific staff of IDEXX

Postdoctoral fellow Stephanie Grainger, PhD, joined the scientific staff of Infraredx

Postdoctoral fellow Donny Hanjaya-Putra, PhD, appointed Assistant Professor, Department of Chemical Engineering, University of Notre Dame

Postdoctoral fellow Jessie Jeon, PhD, was appointed Assistant Professor, Department of Mechanical Engineering, Korea Advanced Institute of Science & Technology (KAIST)

Postdoctoral fellow Venkat Krishnamurthy, PhD, joined the scientific staff of AstraZeneca Pharmaceuticals

Postdoctoral fellow Madhukar Patel, MD, Surgical Resident, Massachusetts General Hospital, received 2015 American College of Surgeons Resident Research Award and NIH Postdoctoral Fellowship Award

Postdoctoral fellow Daniel Wong, MD, Surgical Resident, BIDMC, received 2017 American College of Surgeons Resident Research Award and NIH Postdoctoral Fellowship Award

Selected Research Support

 In situ regeneration of bioactive surfaces: Rechargeable anti-thrombogenic films; NIH, 2013-2017; PI: Elliot L. Chaikof, MD, PhD

Facile synthesis of glycosulfopeptides and related bioconjugates; NIH, 2015-2019; PI: Elliot L. Chaikof, MD, PhD

A PSGL-1 glycopeptide mimetic for treatment of venous thromboembolism; NIH, 2015-2019; PI: Elliot L. Chaikof, MD, PhD

A PSGL-1 glycopeptide mimetic for treatment of metabolic syndrome, NIH, 2016-2021; PI: Elliot L. Chaikof, MD, PhD

Selected Publications

Dorr BM, Ham O, An C, Chaikof EL, Liu DR. Reprogramming the specificity of sortase enzymes by directed evolution. Proc Nat Acad Sci USA 2014; 111:13343–13348.

Angsana J, Chen J, Smith S, Xiao J, Wen J, Liu L, Haller CA, Chaikof EL. Syndecan-1 modulates the motility and resolution responses of macrophages. Arteriosclerosis Thromb Vasc Biol 2015; 35:332-40.

Kim W, Haller CA, Dai E, Wang X, Hagemeyer CE, Liu DR, Peter K, Chaikof EL. Targeted anti-thrombotic protein micelles. Angew Chem Int Ed 2015;54:1461-5.

Krishnamurthy VR, Sardar MYR, Yu Y, Song X, Haller CA, Dai E, Wang X, Hanjaya-Putra D, Sun L, Morikis V, Simon SI, Woods R, Cummings RD, Chaikof EL.  Glycopeptide analogues of PSGL-1 inhibit P-selectin in vitro and in vivo. Nature Communications 2015; 6: 6387.

Patsch C, Challet-Meylan L, Thoma EC, Urich E, Heckel T, Zon LI, Chaikof EL, Gerszten RE, Graf M, Iacone R, Cowan CA. Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells. Nature Cell Biology 2015; 17(8):994-1003.

Ham HO, Qu Z, Haller CA, Dorr BM, Dai E, Kim W, Liu DR, Chaikof EL. In situ regeneration of bioactive coatings enabled by an evolved Staphylococcus aureus sortase A. Nature Communications 2016; 7:11140.

Angsana J, Chen J, Liu L, Haller CA, Chaikof EL. Efferocytosis as a regulator of macrophage chemokine receptor expression and polarization. European J Immunology 2016; 46:1592-1599.

Chen J, Howell C, Haller CA, Patel MS, Ayala P, Moravec KA, Dai E, Liying L, Sotiri I, Aizenberg M, Aizenberg J, Chaikof EL. An immobilized liquid interface prevents device associated bacterial infection in vivo. Biomaterials 2017; 113:80-92.