Research Profile: Elliot L. Chaikof, MD, PhD

Elliot L. Chaikof, MD, PhD

Elliot Chaikof MD PhD
Johnson and Johnson Professor of Surgery
Chair, Department of Surgery

Research Group

Jiaxuan Chen, PhD
Richard Cheng, PhD
Erbin Dai, MD
Pradheep Eradi, PhD
Sayo Eweje
Carolyn A. Haller, PhD
Oki Ham, PhD
Revanth Kosaraju
Liying Liu, MD
Appi Reddy Mandhapati, PhD
Torsten B. Meissner, PhD
David Miranda Nieves, PhD
Diane (Dayoung) Park, PhD
Simon Park, PhD
Rae Rokosh, MD
Daniel Wong, MD

Research Focus

Our laboratory 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
We are currently synthesizing compounds to block inflammatory responses that contribute to deep venous thrombosis, atherosclerosis, metabolic syndrome, inflammatory bowel disease, and cancer metastasis. A number of these drugs are designed to inhibit selectins, which play an important role in the recruitment of leukocytes to inflamed tissue, as well as nuclear receptors that modulate the immune response.

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, including novel synthetic heparins, 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 develop bioprinting approaches, which along with new synthetic collagen and elastin analogues can be assembled with vascular wall cells derived from stem cells to engineer a living artery. We use genome editing to generate “hypoimmunogenic” stem cells that evade the human immune system.

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 without disrupting hemostatic mechanisms or increasing the risk of bleeding.

Genome Editing

Design of delivery systems for in vivo genome editing
Genome editing raises the transformative possibility of curing genetic diseases and installing protective alleles. But major challenges limit the clinical translation of this technology, foremost of which is the difficulty of delivering editing agents to somatic cells in vivo. We are developing new delivery technologies to enable selective editing of target cells with high efficiency and DNA specificity.

Accomplishments 2019-2020

Ongoing collaborations with David Liu, PhD (Broad Institute/Harvard University) have led to a new program directed at the design of delivery systems for in vivo genome editing as part of the NIH Somatic Cell Genome Editing Consortium (SCGE).

Through an established collaboration with Jian Liu, PhD (Chemistry, University of North Carolina) and David Mooney, PhD (Engineering, Harvard University), we have expanded our efforts directed at identifying and harnessing biologically inspired designs to limit blood clotting on artificial surfaces.

We are a member of an NHLBI Consortium Linking Oncology with Thrombosis (CLOT) to determine the underlying biological mechanisms that increase the risk of venous thromboembolism among patients with cancer, in collaboration with Jeffrey Zwicker, MD, PhD, and Robert Flaumenhaft, MD (Hematology, BIDMC). Likewise, we have an ongoing NIH-funded research program to design a new generation of protein drugs that inhibit thrombosis without impairing hemostasis in an ongoing collaboration with Karlheinz Peter, MD, PhD (University of Melbourne, Australia) along with a new collaboration with Karl E. Griswold, PhD, and Chris Bailey-Kellogg, PhD (Computer Science and Engineering, Dartmouth).

We were awarded a $1 million Blavatnik Therapeutics Challenge Award from Harvard Medical School to develop selectin inhibitors for prevention of cancer-associated venous thromboembolism. Ongoing drug discovery efforts include 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 BIDMC Department of Surgery.

Tissue-engineering programs represent collaborations with Axel Guenther, PhD, Professor of Mechanical Engineering at the University of Toronto.

  • Chair for Section 01 (Physical Sciences [Physics/Chemistry], Mathematical Sciences, Computer/Information Sciences, Engineering Sciences), National Academy of Medicine
  • Co-Chair, Health and Technology Interest Group (IG18), National Academy of Medicine
  • Member (ex officio), Committee on Emerging, Science, Technology, and Innovation in Health and Medicine (CESTI), National Academy of Medicine
  • Member, National Materials and Manufacturing Board, Roundtable on Biomedical Engineering Materials and Applications (BEMA), National Academies of Science, Engineering, and Medicine
  • Member, Association of American Physicians

Teaching, Training, and Education

Recipient of the Harvard Medical School Class of 2020 Outstanding Faculty Mentor Award

Presented Robert M. Zollinger Lecture, Ohio State University

Presented Ramon Berguer Lecture, University of Michigan

Selected Research Support

Biomarkers and Mechanisms in Cancer-Associated Thrombosis. NIH/NHLBI, 2018-2023 ($4,465,000); MPI: Elliot Chaikof, MD, PhD; Robert Flaumenhaft, MD, PhD; Jeffrey Zwicker, MD, PhD

The Harvard Translational Glycobiology Career Development Program: Bridging Glycoscience and Clinical Medicine. NIH, 2018-2023 ($4,802,020); MPI: Elliot Chaikof, MD, PhD; Richard D. Cummings, PhD; Robert Sackstein, MD, PhD

Clot-targeted Antithrombotics for Venous Thromboprophylaxis. NIH, 2019-2023 ($1,780,793); PI: Elliot Chaikof, MD, PhD

Delivery Technologies for in Vivo Genome Editing. NIH, 2019-2022 ($2,260,670); PI: Elliot Chaikof, MD, PhD

Selectin Inhibitors for Prevention of Cancer-Associated Venous Thromboembolism. Blavatnik Therapeutics Challenge Award, Harvard Medical School, 2020-2022 ($1,000,000); MPI: Elliot Chaikof, MD, PhD; Lijun Sun, PhD; Richard D. Cummings, PhD

Immunoevasive Engineered Living Blood Vessels. Harvard Stem Cell Institute, 2018-2020 ($100,000); MPI: Elliot Chaikof, MD, PhD; Torsten Meissner, PhD

Selected Publications

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. Nat Commun 2015;6:6387.

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. Nat Commun 2016;7:11140.

Hanjaya-Putra D, Haller C, Wang X, Dai E, Lim B, Liu L, Jaminet P, Yao J, Searle A, Bonnard T, Hagemeyer CE, Peter K, Chaikof EL. Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis. JCI Insight 2018;3(15):e99329.

Chen J, Haller CA, Jernigan FE, Koerner SK, Wong DJ, Wang Y, Cheong JE, Kosaraju R, Kwan J, Park DD, De La Rosa RC, Premji AM, Liu L, Park E, Moss AC, Emili A, Bhasin M, Sun L, Chaikof EL. Modulation of lymphocyte mediated tissue repair by rational design of heterocyclic aryl hydrocarbon receptor agonists. Sci Adv 2020;6(3):eaay8230.

McNamara S, Brudno Y, Miller A, Ham O, Aizenberg M, Chaikof EL, Mooney DJ. Regenerating antithrombotic surfaces through nucleic acid displacement. ACS Biomater Sc Eng 2020;6(4):2159-2166.

Malladi S, Miranda-Nieves D, Leng L, Grainger SJ, Tarabanis C, Nesmith AP, Kosaraju R, Haller CA, Parker KK, Chaikof EL,* Guenther A.* Continuous formation of ultrathin, strong collagen sheets with tunable anisotropy and compaction. ACS Biomater Sc Eng 2020;6(7):4236-4246. *co-senior authors

Bienvenu LA, Maluenda A, McFadyen J, Searle AK, Yu E, Malan E, Haller C, Chaikof EL, Peter K, Wang X. Combined antiplatelet/anticoagulant drug for cardiac ischemia/reperfusion injury. Circ Res 2020;127(9):1211-1213.

Park DD, Chen J, Kudelka MR, Jia N, Haller CA, Kosaraju R, Premji AM, Galizzi M, Nairn AV, Moreman KW, Cummings RD, Chaikof EL. Resident and elicited murine macrophages differ in expression of their glycomes and glycan-binding proteins. Cell Chem Biol 2020; in press.

Wong DJ, Miranda-Nieves D, Nandivada P, Patel MS, Hashimoto DA, Kent D, Gomez-Marquez J, Lin SJ, Feldman HJ, Chaikof EL. The Surgical Program in Innovation (SPIN): A design and prototyping curriculum for surgical trainees. Acad Med 2020; in press.

Krishanu S, Sontheimer EJ, Brooks PJ, Dwinell MR, Gersbach CA, Liu DR,. Murray SA, Tsai SQ, Wilson RC, Anderson DG, Asokan A, Banfield JF, Bankiewicz KS, Bao G, Bulte JWM, Bursac N, Campbell J, Carlson DF, Chaikof EL, et al. Towards safe and effective genome editing therapeutics: The NIH somatic cell genome editing consortium. Nature 2021; in press.