About

Abraham Shaked, MD, PhD, is the Eldridge L. Eliason Professor of Surgery at the University of Pennsylvania and a nationally recognized leader in the field of transplantation. His practice has focused on the surgical treatment of liver and hepatobiliary diseases, and he is one of the most experienced surgeons in the country in adult and pediatric liver transplantation. Dr. Shaked has a special interest in hepatobiliary malignancy and biliary reconstruction. His academic work includes achievements in basic laboratory research and support for clinical science investigation. His laboratory efforts focus on the application of gene transfer technology in the transplant setting. Dr. Shaked is also the Director of the Penn Transplant Institute at the University of Pennsylvania School of Medicine.

Research topics

• Internal medicine
• Medicine
• Endocrinology
• Biology
• Cell biology
• Cancer research
• Gastroenterology
• Cardiology
• Pathology

Selected publications

• Graft-derived VWF drives platelet activation and thrombocytopenia during porcine liver xenotransplantation to brain-dead human recipients

  Journal of Clinical Investigation · 2026-03-10 · 1 citations

  articleOpen access

  BACKGROUNDGenetically engineered porcine livers are being developed as a bridge therapy for acute liver failure, providing detoxification and restoration of hepatic protein synthesis. Severe xenograft-associated thrombocytopenia remains a major limitation, and human mechanistic data are scarce.METHODSPlatelet kinetics were characterized in 3 human decedents undergoing extracorporeal cross-circulation with transgenic porcine livers. Platelet counts, transfusion requirements, and clearance patterns were assessed to distinguish consumption from marrow suppression or hypersplenism. Antibody- and complement-directed inhibitors were administered to test immune-mediated mechanisms. Mechanistic studies focused on porcine von Willebrand factor-dependent (pVWF-dependent) platelet activation, including ex vivo blockade with the anti-VWF nanobody caplacizumab, a VWF-directed antibody fragment that prevents VWF-platelet binding. A fourth decedent received caplacizumab during porcine liver perfusion.RESULTSIn all 3 initial cases, 80%-90% of circulating and transfused platelets were rapidly cleared, a pattern inconsistent with marrow suppression or hypersplenism. Antibody and complement inhibition failed to ameliorate thrombocytopenia. Recipient plasma induced robust pVWF-mediated platelet activation analogous to human type IIb von Willebrand disease, which was completely abrogated ex vivo by caplacizumab. In a fourth decedent treated with caplacizumab, aberrant platelet activation was prevented, although full hematologic recovery was limited by preexisting disseminated intravascular coagulation.CONCLUSIONSEarly thrombocytopenia during porcine liver xenotransplantation appears to be primarily driven by pVWF-mediated platelet activation rather than by classical immune or splenic mechanisms. Targeted VWF blockade with agents such as caplacizumab may mitigate platelet loss and improve the safety profile of extracorporeal porcine liver support in acute liver failure.

  PublisherDOI

• Expanded chromatin accessibility mapping explains genetic variation associated with complex traits in liver

  The American Journal of Human Genetics · 2026-02-01

  articleOpen access
  PublisherOA PDFDOI

• 177d: SIMULTANEOUS QUANTIFICATION OF FUNCTION OF NATIVE HUMAN LIVER AND PORCINE LIVER IN AN EXTRACORPOREAL CIRCUIT DERIVED FROM THE BLOOD CONCENTRATIONS OF INTRAVENOUSLY INJECTED 13C-CHOLATE

  Gastroenterology · 2025-05-01

  article1st authorCorresponding
  PublisherDOI

• TOP-507 Quantifying liver function by cholate clearance in extracorporeal circuits with a genetically modified porcine liver and brain-dead human decedent

  Journal of Hepatology · 2025-05-01

  article1st authorCorresponding
  PublisherDOI

• B-Cell Subset Representation Predicts SARS-CoV-2 Vaccine Response in Solid Organ Transplant Recipients

  The Journal of Infectious Diseases · 2025-06-03 · 3 citations

  articleOpen access

  BACKGROUND: Solid organ transplant recipients (SOTRs) suffer increased morbidity and mortality due, in part, to chronic immunosuppression. The determination of an individual's immune competence is currently difficult but would improve risk assessment and inform medical decisions. We reasoned that correlating qualitative and quantitative measures of the B-cell compartment with serologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination would reveal novel B-cell-based predictors of immune competence. METHODS: We performed an integrated analysis of B-cell phenotypes, serology, and antibody repertoires in heart, lung, liver, kidney, and multiorgan transplant recipients and healthcare worker (HCW) controls (62 individuals total). We utilized K-means clustering and correlation analyses to identify B-cell features that correlated with vaccine serology. RESULTS: K-means clustering identified 3 distinct B-cell compartment-based groups in SOTRs, which correlated with serum responses to SARS-CoV-2 vaccination. Group 1 SOTRs had a naive-dominant circulating B-cell pool and serologic responses closest to HCWs. Group 2 SOTRs had reduced naive but hyperexpanded memory B cells (MBCs) and variable vaccine responses that segregated by immunosuppression. Group 3 SOTRs had lymphopenia across B-cell subsets and poor serologic responses. Antibody repertoire analysis showed reduced clonal diversity across SOTRs, regardless of MBC numbers. Even in SOTRs with the largest immune responses, vaccine-specific B cells showed evidence of reduced maturation and clonal diversity. CONCLUSIONS: These findings reveal a hierarchy of B-cell impairment in SOTRs that can be measured rapidly, with implications for immune monitoring and intervention in immunocompromised individuals.

  PublisherOA PDFDOI

• Expanded Chromatin Accessibility Mapping Explains Genetic Variation Associated with Complex Traits in Liver

  medRxiv · 2025-09-15

  preprintOpen access

  Genome-wide association studies (GWAS) have identified thousands of loci associated with a variety of common, complex human traits. Recent efforts have focused on characterizing chromatin accessibility to discover regulatory elements that modify the expression of nearby genes, suggesting that trait associations are mediated through changes in gene regulation. Genetic variants associated with differences in chromatin accessibility, known as chromatin accessibility quantitative trait loci (caQTLs), are established contributors to gene expression differences, providing mechanistic hypotheses for signals identified by GWAS. Using the assay for transposase-accessible chromatin with sequencing (ATAC-seq), we assessed chromatin accessibility in 189 diverse human liver samples, identifying over two million accessible chromatin regions enriched for gene regulatory features and, in 175 of these samples, over 14,000 caQTLs. Focusing subsequently on liver-relevant complex traits, we obtained publicly available blood lipids GWAS data and identified 157 loci where caQTLs, expression quantitative trait loci (eQTLs), and GWAS signals colocalized. This generated specific molecular hypotheses about regulatory elements, affected genes, and, in some cases, implicated transcription factors. Finally, we enumerated the set of blood lipid trait signals that lack an obvious proposed mechanism beyond catalogs of liver caQTLs and eQTLs. After integrating 10 multi-omic QTL regulatory mechanism datasets whilst considering limitations in statistical power, we found that approximately 20% of blood lipid GWAS signals lacked a statistical link to a proposed mechanism. Our results demonstrate the value of integrating multiple genomic datasets to improve understanding of GWAS signals, while emphasizing the need for additional experimental approaches to fully characterize complex trait associations.

  PublisherOA PDFDOI

• Analytical Validation of a Serum miRNA RT-qPCR Assay for Monitoring Allograft Liver Rejection

  American Journal of Transplantation · 2025-08-01

  articleSenior author
  PublisherDOI

• Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways

  medRxiv · 2025-09-18 · 1 citations

  preprintOpen access

  Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases, 2.36M controls) and HCC (6,680 cases, 1.76M controls), we identified 27 loci associated with cirrhosis (10 novel) and 11 with HCC (three novel). Three novel cirrhosis loci were replicated in independent cohorts (e.g. FGF21, RPTOR, and IFNL3/4). Fifteen cirrhosis loci exhibited differential effects on cirrhosis risk via underlying etiologies, and six HCC loci influenced HCC risk indirectly via cirrhosis. In a gene-burden analysis of rare variants from whole-genome sequencing data in the VA Million Veteran Program (n=102,677), we identified GSTA5 as a novel cirrhosis-associated gene, while APOB and ATP9B were associated with and replicated for HCC. A high genetic risk score for cirrhosis was associated with a nearly doubled risk of CLD progressing to cirrhosis (HR=1.94, P=2x10-68) and of cirrhosis progressing to HCC (HR=1.65, P=7x10-08). Finally, among individuals with chronic hepatitis C who underwent antiviral therapy, cirrhosis risk was modified by variants in PNPLA3, IFNL3/4, and CD81 following pegylated interferon-α therapy, and by APOE lead variant following direct-acting antiviral therapy. These findings provide new insights into the complex genetic architecture of CLD progression with potential clinical and therapeutic implications.

  PublisherOA PDFDOI

• Donor and recipient genetics: Implications for the development of posttransplant diabetes mellitus

  American Journal of Transplantation · 2024-05-21 · 3 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• 12442 Effectiveness Of An Electronic Decision Support Algorithm To Optimize Recommendation Of SGLT2i And GLP-1RA In Patients With Type 2 Diabetes Upon Discharge From Internal Medicine Wards

  Journal of the Endocrine Society · 2024-10-01

  articleOpen access

  Abstract Disclosure: E. Jaffe: None. I. Ayalon-Dangur: Grant Recipient; Self; Boehringer Ingelheim. A. Grossman: None. H. Hendel: None. Y. Oved: None. A. Shaked: None. I. Shimon: None. B. Basharim: None. M. Abo Molhem: None. R. McNeil: None. R. Abuhasira: None. T. Shitrit: None. L. Azulay Gitter: None. R. El Saleh: None. T. Shochat: None. N. Eliakim-Raz: None. Background: Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality. Current guidelines recommend the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with T2DM with or at high risk for cardiovascular disease to reduce mortality. Despite the established benefit, many studies found low treatment rates with these medications in eligible patients. The aim of our study is to examine the effectiveness of a clinical decision support (CDS) algorithm that was developed in our institution, in improving the recommendation rate of SGLT2i and GLP-1RA upon discharge from hospitalization in internal medicine wards. Methods: Our algorithm was developed to automatically recommend SGLT2i and GLP-1RA for T2DM patients based on current guidelines. Data was collected from electronic medical records of all T2DM patients ≥18 years old who were eligible for SGLT2i or GLP-1RA and hospitalized for any reason in one of five internal medicine wards in Beilinson Hospital. The primary outcome was to evaluate the rate of physician recommendation of SGLT2i or GLP-1RA at hospital discharge for eligible patients pre-algorithm implementation (January 2021-December 2021) versus post-algorithm implementation (April 2023-September 2023). Results: A total of 1318 patients were included in the pre-algorithm group and 970 were included in the post-algorithm group. Median age was 75 and 73 years in the pre- and post-algorithm groups, respectively. In the pre-algorithm group, 62% were males vs 60% in the post-algorithm group. Median length of hospitalization was three days and four days in the pre- and post-algorithm groups, respectively. The rate of SGLT2i and GLP-1RA recommendation for eligible patients was 8.50% (112 of 1318 patients) in the pre-algorithm group and 22.68% (220 of 970 patients) in the post-algorithm group. The odds ratio of the recommendation rate in the post vs pre-algorithm group was 3.151, 95% confidence interval 2.467– 4.025, p<0.0001. Conclusion: The results of this study demonstrate the benefit of an algorithm as part of a CDS system to improve recommendation rates of SGLT2i and GLP-1RA for eligible patients upon discharge from hospitalization. Future studies should assess the impact of the algorithm on prescription rates, patient adherence, and long-term outcomes. Presentation: 6/2/2024

  PublisherOA PDFDOI

Recent grants

• NIH Grant U01DK062494

  NIH · $3.3M · 2015

• NIH Grant R29DK046311

  NIH · $552k · 1998

• NIH Grant U01AI063589

  NIH · $14.4M · 2011

Frequent coauthors

• Kim M. Olthoff

  University of Pennsylvania

  207 shared

• David E.R. Sutherland

  Loyola University Medical Center

  50 shared

• Kazue Ozawa

  50 shared

• R Gran- Stein

  University of Louisville Hospital

  49 shared

• Jean Tchervenkov

  McGill University Health Centre

  49 shared

• Ning Wang

  Second Affiliated Hospital of Zhejiang University

  49 shared

• R Su- Perina

  Unifor

  49 shared

• T.S. Ravikumar

  Jawaharlal Institute of Post Graduate Medical Education and Research

  49 shared

Labs

• Abraham Shaked LaboratoryPI

Education

• M.D.

  Hebrew University, Israel

  1982

• Ph.D.

  City University of New York

  1989