About

Biju Parekkadan is an Associate Professor in the Department of Biomedical Engineering at Rutgers University. His research interests include cell therapy, genetic engineering, biomaterials science and tissue engineering, bioreactors, drug delivery, biomanufacturing, systems and computational biology. His work focuses on advancing understanding and development in these areas to improve biomedical applications and therapies.

Research topics

• Biology
• Medicine
• Computational biology
• Genetics
• Immunology
• Cancer research
• Cell biology
• Internal medicine
• Pathology
• Biotechnology
• Chemistry
• Pharmacology
• Virology
• Ecology
• Molecular biology

Selected publications

• Acellular Normothermic Machine Perfusion Does not Exacerbate Acute Rejection in Rodent Vascularized Composite Allografts

  Transplantation Direct · 2026-05-06

  articleOpen accessCorresponding

  Background: Vascularized composite allotransplantation faces significant challenges, including limited preservation time and high rates of acute rejection because of the ischemia susceptibility of muscle and immunogenicity of skin. However, no studies have investigated whether normothermic machine perfusion (NMP) has an effect on acute rejection compared with static cold storage (SCS). Methods: Heterotopic hindlimb transplants were performed in a full-mismatch model after 6 h of SCS or NMP. Postoperative assessments included clinical scoring, histological examination, cytokine profiling, and flow cytometry of splenocytes and lymphocytes at the end of the study. Results: = 0.03). Notably, histology indicated delayed rejection, with Banff scores showing severe rejection from POD2 in the SCS group and from POD6 in the NMP group. Cytokine profiling demonstrated early upregulation of anti-inflammatory interleukin-10 in the NMP group at POD1, and flow cytometry showed a reduction in B cell populations. Conclusions: While NMP is not a cure-all, it is associated with a delayed onset of acute rejection compared with SCS in a full-mismatch rodent vascularized composite allotransplantation model. Future studies should focus on analysis earlier in the rejection process and on long-term graft survival to further elucidate the mechanism of the effect of NMP on the immune response.

  PublisherDOI

• Genetically engineered organs for early reporting of transplant rejection

  Molecular Therapy · 2025-10-15 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• 11. Early Reporting of Transplant Rejection: Genetically Engineered ‘Smart-Organs’ Featuring Diagnostic Capabilities

  Transplantation · 2025-06-01

  article

  Introduction: Early detection of organ transplant rejection is hindered by the limitations of existing diagnostic tools. Blood tests lack sensitivity and specificity, while biopsies are invasive and pose procedural risks. To address these challenges, this study explores an innovative approach that combines gene therapy and machine perfusion to create genetically engineered biosensor cells capable of detecting and responding to inflammatory events with high sensitivity and specificity. Achieving long-term genetic modification is also explored, with the goal of achieving non-invasive and early detection of rejection in transplanted organs. Methods: Vascularized composite allografts (VCA) were genetically modified ex vivo using lentiviral vectors as gene delivery systems during ex vivo machine perfusion (Fig.1A). To show long-term genetic modification, a constitutive (EF1a) promoter was used in a non-rejection transplant model. Second, in a partial mismatch transplant model, VCAs were transduced using an inflammation-responsive element designed to detect rejection events, releasing a blood-based biomarker, Gaussia Luciferase (GLuc). Plasma and biopsies were collected in the postoperative period. Results: Genetically modified VCAs demonstrated transgene expression for over 300 days in the non-rejection model (Fig.1B). The inflammation-responsive system enabled detection of rejection by bioluminescence six days before histological evidence of rejection (Fig.1C). GLuc was reliably measurable in the bloodstream as a biomarker at the beginning of rejection episodes (Fig.1D). Under immunosuppression, rejection animals showed GLuc levels comparable to controls. Conclusions: This study provides the first evidence that genetically modifying organs during machine perfusion can enable long-term transgene expression and improve diagnostic capabilities in organ transplantation. Integration of a synthetic promoter and inflammation-responsive elements facilitated earlier and noninvasive detection rejection, with potential implications for improving long-term graft survival and enhancing transplant management strategies.

  PublisherDOI

• Designer Organs: Ethical Genetic Modifications in the Era of Machine Perfusion

  Annual Review of Biomedical Engineering · 2025-01-28 · 3 citations

  reviewOpen access

  Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant. EVMP has the potential to enhance genetic engineering efficiency, improve graft survival, and reduce posttransplant complications. This will enable genetic modifications with a vast variety of applications, while raising questions on the ethics and regulation of this emerging technology. This review provides an in-depth discussion of current methodologies for delivering genetic vectors to transplantable organs, particularly focusing on the enabling role of EVMP. Organ-by-organ analysis and key characteristics of various vector and treatment options are assessed. We offer a road map for research and clinical translation, arguing that achieving scientific benchmarks while creating anticipatory governance is necessary to secure societal benefit from this technology.

  PublisherDOI

• Ex vivo machine perfusion as a platform for lentiviral gene delivery in rat livers

  Utrecht University Repository (Utrecht University) · 2025-07-01

  articleOpen access

  Developing new strategies for local monitoring and delivery of immunosuppression is critical to making allografts safer and more accessible. Ex vivo genetic modification of grafts using machine perfusion presents a promising approach to improve graft function and modulate immune responses while minimizing risks of off-target effects and systemic immunogenicity in vivo. This proof-of-concept study demonstrates the feasibility of using normothermic machine perfusion (NMP) to mimic in vitro conditions for effective gene delivery. In this study, lentiviral vectors encoding the secreted biomarker Gaussia Luciferase (GLuc) and red fluorescent protein (RFP) were introduced ex vivo to rodent livers during a 72-h machine perfusion protocol. After an initial 24-h exposure to viral vectors, the organs were maintained in perfusion for an additional 48 h to monitor gene expression, aligning with in vitro benchmarks. Control livers were perfused in similar fashion, but without viral injections. Virally perfused livers exhibited nearly a 10-fold increase in luminescence compared to controls (p < 0.0001), indicating successful genetic modification of the organs. These findings validate the use of machine perfusion systems and viral vectors to genetically engineer whole organs ex vivo, laying the groundwork for a broad range of applications in transplantation through genetic manipulation of organ systems. Future studies will focus on refining this technology to enhance precision in gene expression and explore its implications for clinical translation.

  Publisher

• Designer Organs:Ethical Genetic Modifications in the Era of Machine Perfusion

  Utrecht University Repository (Utrecht University) · 2025-05-01

  articleOpen access

  Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant. EVMP has the potential to enhance genetic engineering efficiency, improve graft survival, and reduce posttransplant complications. This will enable genetic modifications with a vast variety of applications, while raising questions on the ethics and regulation of this emerging technology. This review provides an in-depth discussion of current methodologies for delivering genetic vectors to transplantable organs, particularly focusing on the enabling role of EVMP. Organ-by-organ analysis and key characteristics of various vector and treatment options are assessed. We offer a road map for research and clinical translation, arguing that achieving scientific benchmarks while creating anticipatory governance is necessary to secure societal benefit from this technology.

  Publisher

• Evaluation of Purification Methods for Minimizing Transgene Expression Background During Viral Manufacturing

  Human Gene Therapy · 2025-03-19 · 1 citations

  articleOpen accessSenior authorCorresponding

  Gene therapy has emerged as a promising therapeutic avenue, offering targeted treatments for various diseases. Purification of viral vectors presents a pivotal challenge, demanding the removal of impurities while preserving integrity and potency. During manufacturing, producer cells in transfection systems can be transiently transfected or retro-infected by the viral vectors they have just produced—a process referred to as “retro-transduction”—leading them to express the transgenes of interest. This can be a significant source of contamination in the viral solution pool, particularly when the transgenes encode extracellular, secreted proteins, resulting in cytotoxicity and reduced viral potency. Herein, we aimed to evaluate the efficiency of different viral purification systems commonly used in academic and industry settings in removing the transgene background from viral solutions. The efficiency of each system was assessed based on the levels of the secreted transgene Gaussia Luciferase (GLuc), which can be quickly detected in a solution and served as a readout for transgene background contamination in the viral pool during downstream processing. Through a systematic evaluation of purification methods, we identified the most effective approaches for producing pure viral batches with minimal transgene background, all while preserving viral potency and functionality. Our study revealed superior performance of batches that underwent purification via tangential flow filtration, which yielded over 90% reduction in GLuc background and the highest transduction efficiency rates. This work provides significant insights for advancing gene therapy applications that rely on the production of viral vectors encoding secreted transgenes.

  PublisherOA PDFDOI

• Cutaneous suction-mediated transfection in mice for delivery of DNA-encoded vaccines and proteins

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-11 · 1 citations

  preprintOpen access

  Abstract An important step to fulfill the functionalities of DNA vaccines and therapeutics is transfection in vivo to produce the encoded antigens or therapeutic proteins. A cutaneous suction-based method has demonstrated effectiveness in many animal models and has been successfully applied in human clinical trials, but has not been extended to mouse models, where numerous disease models, transgenic strains, and murine-specific reagents exist. The current work establishes and optimizes methods for cutaneous suction-mediated DNA transfection in mice. By adapting a smaller cup diameter and smaller injection volume, the challenges of skin hyperelasticity and decreased skin thickness can be effectively addressed, and vaccinating mice with the GLS-5310 SARS-CoV-2 DNA vaccine yielded high levels of binding antibody and T cell responses. Additionally, suction following injection of a novel pVAX1-based expression vector yielded systemic levels of a SEAP transgene. Thus, suction-mediated delivery of nucleic acid-based therapies and vaccines can be a valuable tool for the study in pre-clinical mouse models.

  PublisherOA PDFDOI

• In Vivo Evolution of <i>Lacticaseibacillus rhamnosus</i> GG Leads to Prolonged Persistence in the Digestive Tract

  Food Bioengineering · 2025-03-01 · 3 citations

  articleOpen accessSenior authorCorresponding

  ABSTRACT This study explored in vivo evolution as a method to generate evolutionary clones of Lacticaseibacillus rhamnosus GG, a renowned probiotic organism found in many food supplements, with improved persistence in the intestinal tract. L. rhamnosus GG was autologously gavaged to mice and subsequently selected and grown ex vivo after passage through the intestinal tract to form two evolutionary isolates of the bacteria. A longer retention time (nearly 3×) and a slower elimination rate of the bacteria in the mouse gut were observed with each evolution. The evolutionary isolates were further characterized for key traits such as bile salt resistance, epithelial cell binding, and genetic alterations to understand potential changes to known persistence mechanisms. Finally, a series of heterologous gavages were performed to determine if the increased retention of the evolutionary variants were because of animal‐specific host adaptations. Similar results were seen following heterologous gavages, supporting the concept that intrinsic changes to Lacticaseibacillus occurred. Based on these findings, in vivo evolution shows promise as a technique to generate probiotic strains with improved traits for gut retention as compared to the wild type.

  PublisherOA PDFDOI

• Early Reporting of Transplant Rejection: Genetically Engineered ‘Smart-Organs’ Featuring Diagnostic Capabilities

  American Journal of Transplantation · 2025-08-01

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• Artificial, Humanized Stem Cell Niches

  NIH · $6.0M · 2011–2023

• NIH Grant K01DK087770

  NIH · $544k · 2016

• NIH Grant R21AI134116

  NIH · $463k · 2021

• Genetic-engineered control of the immunogeneic state of vascular composite allografts during preservation

  NIH · $3.1M · 2021–2029

• A Functional genomics platform with integrated library cloning and molecular display

  NIH · $1.4M · 2018–2022

Frequent coauthors

• Martin L. Yarmush

  Shriners Hospitals for Children - Boston

  318 shared

• Matthew Li

  People's Hospital of Cangzhou

  175 shared

• Arno W. Tilles

  Sentien (United States)

  137 shared

• Jack M. Milwid

  93 shared

• Mehmet Toner

  Harvard University

  89 shared

• Amy Singleton

  Mercy Health

  87 shared

• Daan van Poll

  University College London

  85 shared

• Danika Khong

  University Medical Center Hamburg-Eppendorf

  73 shared

Labs

• Rutgers Department of Biomedical EngineeringPI

Education

• Ph.D., Biomedical Engineering

  University of Florida

  2004

• M.S., Biomedical Engineering

  University of Florida

  2000

• B.S., Mechanical Engineering

  University of Florida

  1998