Academic Appointments

Boards, Advisory Committees, Professional Organizations

  • Member, American Association of Laboratory Animal medicine (2011 - Present)
  • Diplomate, American College of Laboratory Animal Medicine (2014 - Present)

Professional Education

  • DVM, Educational Commission for Foreign Veterinary Graduates, Veterinary Medicine (2013)
  • VetMB, University of Cambridge, Veterinary Medicine (2011)
  • BA, University of Cambridge, Zoology (2008)

All Publications

  • A neonatal leporine model of age-dependent natural heart regeneration after myocardial infarction. The Journal of thoracic and cardiovascular surgery Wang, H., Hironaka, C. E., Mullis, D. M., Lucian, H. J., Shin, H. S., Tran, N. A., Thakore, A. D., Anilkumar, S., Wu, M. A., Paulsen, M. J., Zhu, Y., Baker, S. W., Woo, Y. J. 2021


    OBJECTIVES: Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction.METHODS: New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n=94), postnatal day 4 (n=11), or postnatal day 7 (n=52). Hearts were explanted 1day postsurgery to confirm ischemic injury, at 1week postsurgery to assess cardiomyocyte proliferation, and at 3weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean±standard deviation.RESULTS: Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3%±5.4% vs 42.3%±4.7%, P=.9984). Echocardiography confirmed severely reduced ejection fraction at 1day after postnatal day 1 myocardial infarction (33.7%±5.3% vs 65.2%±5.5% for postnatal day 1 sham, P=.0001), but no difference at 3weeks after postnatal day 1 myocardial infarction (56.0%±4.0% vs 58.0%±3.3% for postnatal day 1 sham, P=.2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2%±1.8% vs 58.5%±5.8% for postnatal day 4 sham, P=.0109) and postnatal day 7 myocardial infarction (39.0%±7.8% vs 60.2%±5.0% for postnatal day 7 sham, P<.0001). At 3weeks after infarction, fibrotic scar represented 5.3%±1.9%, 14.3%±4.9%, and 25.4%±13.3% of the left ventricle area in the postnatal day 1, postnatal day 4, and postnatal day 7 groups, respectively. An increased proportion of peri-infarct cardiomyocytes expressed Ki67 (15.9%±1.8% vs 10.2%±0.8%, P=.0039) and aurora B kinase (4.0%±0.9% vs 1.5%±0.6%, P=.0088) after postnatal day 1 myocardial infarction compared with sham, but no increase was observed after postnatal day 7 myocardial infarction.CONCLUSIONS: A neonatal leporine myocardial infarction model reveals that newborn rabbits are capable of age-dependent natural heart regeneration.

    View details for DOI 10.1016/j.jtcvs.2021.08.013

    View details for PubMedID 34649718

  • Full closed loop open-source algorithm performance comparison in pigs with diabetes. Clinical and translational medicine Lal, R. A., Maikawa, C. L., Lewis, D., Baker, S. W., Smith, A. A., Roth, G. A., Gale, E. C., Stapleton, L. M., Mann, J. L., Yu, A. C., Correa, S., Grosskopf, A. K., Liong, C. S., Meis, C. M., Chan, D., Garner, J. P., Maahs, D. M., Buckingham, B. A., Appel, E. A. 2021; 11 (4): e387


    Understanding how automated insulin delivery (AID) algorithm features impact glucose control under full closed loop delivery represents a critical step toward reducing patient burden by eliminating the need for carbohydrate entries at mealtimes. Here, we use a pig model of diabetes to compare AndroidAPS and Loop open-source AID systems without meal announcements. Overall time-in-range (70-180mg/dl) for AndroidAPS was 58% ± 5%, while time-in-range for Loop was 35% ± 5%. The effect of the algorithms on time-in-range differed between meals and overnight. During the overnight monitoring period, pigs had an average time-in-range of 90% ± 7% when on AndroidAPS compared to 22% ± 8% on Loop. Time-in-hypoglycemia also differed significantly during the lunch meal, whereby pigs running AndroidAPS spent an average of 1.4% (+0.4/-0.8)% in hypoglycemia compared to 10% (+3/-6)% for those using Loop. As algorithm design for closed loop systems continues to develop, the strategies employed in the OpenAPS algorithm (known as oref1) as implemented in AndroidAPS for unannounced meals may result in a better overall control for full closed loop systems.

    View details for DOI 10.1002/ctm2.387

    View details for PubMedID 33931977

  • A fluorescence sandwich immunoassay for the real-time continuous detection of glucose and insulin in live animals. Nature biomedical engineering Poudineh, M., Maikawa, C. L., Ma, E. Y., Pan, J., Mamerow, D., Hang, Y., Baker, S. W., Beirami, A., Yoshikawa, A., Eisenstein, M., Kim, S., Vuckovic, J., Appel, E. A., Soh, H. T. 2020


    Biosensors that continuously measure circulating biomolecules in real time could provide insights into the health status of patients and their response to therapeutics. But biosensors for the continuous real-time monitoring of analytes in vivo have only reached nanomolar sensitivity and can measure only a handful of molecules, such as glucose and blood oxygen. Here we show that multiple analytes can be continuously and simultaneously measured with picomolar sensitivity and sub-second resolution via the integration of aptamers and antibodies into a bead-based fluorescence sandwich immunoassay implemented in a custom microfluidic chip. After an incubation time of 30s, bead fluorescence is measured using a high-speed camera under spatially multiplexed two-colour laser illumination. We used the assay for continuous quantification of glucose and insulin concentrations in the blood of live diabetic rats to resolve inter-animal differences in the pharmacokinetic response to insulin as well as discriminate pharmacokinetic profiles from different insulin formulations. The assay can be readily modified to continuously and simultaneously measure other blood analytes in vivo.

    View details for DOI 10.1038/s41551-020-00661-1

    View details for PubMedID 33349659

  • Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-Based Therapeutic Drug Monitoring IEEE JOURNAL OF SOLID-STATE CIRCUITS Chien, J., Baker, S. W., Soh, H., Arbabian, A. 2020; 55 (11): 2914–29
  • Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-based Therapeutic Drug Monitoring. IEEE journal of solid-state circuits Chien, J. C., Baker, S. W., Soh, H. T., Arbabian, A. 2020; 55 (11): 2914-2929


    In this paper, we present the design and the analysis of an electrochemical circuit for measuring the concentrations of therapeutic drugs using structure-switching aptamers. Aptamers are single-stranded nucleic acids, whose sequence is selected to exhibit high affinity and specificity toward a molecular target, and change its conformation upon binding. This property, when coupled with a redox reporter and electrochemical detection, enables reagent-free biosensing with a sub-minute temporal resolution for in vivo therapeutic drug monitoring. Specifically, we design a chronoamperometry-based electrochemical circuit that measures the direct changes in the electron transfer (ET) kinetics of a methylene blue reporter conjugated at the distal-end of the aptamer. To overcome the high-frequency noise amplification issue when interfacing with a large-size (> 0.25 mm2) implantable electrode, we present a sample-and-hold (S/H) circuit technique in which the desired electrode potentials are held onto noiseless capacitors during the recording of the redox currents. This allows disconnecting the feedback amplifiers to avoid its noise injection while reducing the total power consumption. A prototype circuit implemented in 65-nm CMOS demonstrates a cell-capacitance-insensitive input-referred noise (IRN) current of 15.2 pArms at a 2.5-kHz filtering bandwidth. We tested our system in human whole blood samples and measured the changes in the ET kinetics from the redox-labeled aptamers at different kanamycin concentrations. By employing principal component analysis (PCA) to compensate for the sampling errors, we report a molecular noise floor (at SNR = 1) of 3.1 µM with sub 1-sec acquisition time at 0.22-mW power consumption.

    View details for DOI 10.1109/jssc.2020.3020789

    View details for PubMedID 33343021

    View details for PubMedCentralID PMC7742970

  • Transient-mixed Chimerism With Nonmyeloablative Conditioning Does Not Induce Liver Allograft Tolerance in Nonhuman Primates. Transplantation Chaudhry, S., Kato, Y., Weiner, J., Alonso-Guallart, P., Baker, S., Woodland, D. C., Lefkowitch, J. H., Duran-Struuck, R., Sondermeijer, H. P., Zitsman, J., Sears, M. L., Wu, A., Karolewski, B., Houck, P. J., Martinez, M., Kato, T., Sykes, M., Griesemer, A. D. 2020; 104 (8): 1580-1590


    Although short-term outcomes for liver transplantation have improved, patient and graft survival are limited by infection, cancer, and other complications of immunosuppression. Rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. Tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. Since the liver is considered to be tolerogenic, we tested the hypothesis that the renal transplant transient chimerism protocol would induce liver tolerance.Seven cynomolgus macaques received immune conditioning followed by simultaneous donor bone marrow and liver transplantation. The more extensive liver surgery required minor adaptations of the kidney protocol to decrease complications. All immunosuppression was discontinued on postoperative day (POD) 28. Peripheral blood chimerism, recipient immune reconstitution, liver function tests, and graft survival were determined.The level and duration of chimerism in liver recipients were comparable to those previously reported in renal transplant recipients. However, unlike in the kidney model, the liver was rejected soon after immunosuppression withdrawal. Rejection was associated with proliferation of recipient CD8 T effector cells in the periphery and liver, increased serum interleukin (IL)-6 and IL-2, but peripheral regulatory T cell (Treg) numbers did not increase. Antidonor antibody was also detected.These data show the transient chimerism protocol does not induce tolerance to livers, likely due to greater CD8 T cell responses than in the kidney model. Successful tolerance induction may depend on greater control or deletion of CD8 T cells in this model.

    View details for DOI 10.1097/TP.0000000000003263

    View details for PubMedID 32732835

  • Electrophysiologic Conservation of Epicardial Conduction Dynamics After Myocardial Infarction in Newborn Piglets Wang, H., Pong, T., Lucian, H., Aparicio-Valenzuela, J., Tada, Y., Sakhamuri, S., Baker, S. W., Tran, N. A., Paulsen, M. J., Zhu, Y., Lee, A. M., Woo, Y. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients. Science translational medicine Mann, J. L., Maikawa, C. L., Smith, A. A., Grosskopf, A. K., Baker, S. W., Roth, G. A., Meis, C. M., Gale, E. C., Liong, C. S., Correa, S., Chan, D., Stapleton, L. M., Yu, A. C., Muir, B., Howard, S., Postma, A., Appel, E. A. 2020; 12 (550)


    Insulin has been used to treat diabetes for almost 100 years; yet, current rapid-acting insulin formulations do not have sufficiently fast pharmacokinetics to maintain tight glycemic control at mealtimes. Dissociation of the insulin hexamer, the primary association state of insulin in rapid-acting formulations, is the rate-limiting step that leads to delayed onset and extended duration of action. A formulation of insulin monomers would more closely mimic endogenous postprandial insulin secretion, but monomeric insulin is unstable in solution using present formulation strategies and rapidly aggregates into amyloid fibrils. Here, we implement high-throughput-controlled radical polymerization techniques to generate a large library of acrylamide carrier/dopant copolymer (AC/DC) excipients designed to reduce insulin aggregation. Our top-performing AC/DC excipient candidate enabled the development of an ultrafast-absorbing insulin lispro (UFAL) formulation, which remains stable under stressed aging conditions for 25 ± 1 hours compared to 5 ± 2 hours for commercial fast-acting insulin lispro formulations (Humalog). In a porcine model of insulin-deficient diabetes, UFAL exhibited peak action at 9 ± 4 min, whereas commercial Humalog exhibited peak action at 25 ± 10 min. These ultrafast kinetics make UFAL a promising candidate for improving glucose control and reducing burden for patients with diabetes.

    View details for DOI 10.1126/scitranslmed.aba6676

    View details for PubMedID 32611683

  • Tumor shedding and metastatic progression after tumor excision in patient-derived orthotopic xenograft models of triple-negative breast cancer. Clinical & experimental metastasis Razmara, A. M., Sollier, E., Kisirkoi, G. N., Baker, S. W., Bellon, M. B., McMillan, A., Lemaire, C. A., Ramani, V. C., Jeffrey, S. S., Casey, K. M. 2020


    Patient-derived orthotopic xenograft (PDOX) models have been verified as a useful method for studying human cancers in mice. Previous studies on the extent of metastases in these models have been limited by the necessity of welfare euthanasia (primary tumors reaching threshold size), at which point metastases may only be micrometers in diameter, few in number, and solely identified by step-sectioning of formalin-fixed paraffin-embedded tissue. These small micro-metastases are less suitable for many downstream molecular analyses than macro-metastases. Resection of the primary tumor by survival surgery has been proven to allow further time for metastases to grow. Although PDOX models of triple-negative breast cancer (TNBC) shed circulating tumor cells (CTCs) into the bloodstream and metastasize, similar to human TNBC, little data has been collected in these TNBC PDOX models regarding the association between CTC characteristics and distant metastasis following excision of the primary tumor xenograft. This study assembles a timeline of PDOX tumor shedding and metastatic tumor progression before and after tumor excision surgery. We report the ability to use tumorectomies to increase the lifespan of TNBC PDOX models with the potential to obtain larger metastases. CTC clusters and CTCs expressing a mesenchymal marker (vimentin) were associated with metastatic burden in lung and liver. The data collected through these experiments will guide the further use of PDOX models in studying metastatic TNBC.

    View details for DOI 10.1007/s10585-020-10033-3

    View details for PubMedID 32335861

  • Multi-phase catheter-injectable hydrogel enables dual-stage protein-engineered cytokine release to mitigate adverse left ventricular remodeling following myocardial infarction in a small animal model and a large animal model Cytokine Steele, A. N., Paulsen, M. J., Wang, H., Stapleton, L. M., Lucian, H. J., Eskandari, A., Hironaka, C. E., Farry, J. M., Baker, S. W., Thakore, A. D., Jaatinen, K. J., Tada, Y., Hollander, M. J., Williams, K. M., Seymour, A. J., Totherow, K. P., Yu, A. C., Cochran, J. R., Appel, E. A., Woo, Y. J. 2020; 127

    View details for DOI 10.1060/154974

  • In Vivo Validation of Restored Chordal Biomechanics After Mitral Ring Annuloplasty in a Rare Ovine Case of Natural Chronic Functional Mitral Regurgitation. Journal of cardiovascular development and disease Wang, H. n., Paulsen, M. J., Imbrie-Moore, A. M., Tada, Y. n., Bergamasco, H. n., Baker, S. W., Shudo, Y. n., Ma, M. n., Woo, J. Y. 2020; 7 (2)


    Mitral valve chordae tendineae forces are elevated in the setting of mitral regurgitation (MR). Ring annuloplasty is an essential component of surgical repair for MR, but whether chordal forces are reduced after mitral annuloplasty has never been validated in vivo. Here, we present an extremely rare ovine case of natural, severe chronic functional MR, in which we used force-sensing fiber Bragg grating neochordae to directly measure chordal forces in the baseline setting of severe MR, as well as after successful mitral ring annuloplasty repair. Overall, our report is the first to confirm in vivo that mitral ring annuloplasty reduces elevated chordae tendineae forces associated with chronic functional MR.

    View details for DOI 10.3390/jcdd7020017

    View details for PubMedID 32429298

  • A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs. Nature biomedical engineering Maikawa, C. L., Smith, A. A., Zou, L. n., Roth, G. A., Gale, E. C., Stapleton, L. M., Baker, S. W., Mann, J. L., Yu, A. C., Correa, S. n., Grosskopf, A. K., Liong, C. S., Meis, C. M., Chan, D. n., Troxell, M. n., Maahs, D. M., Buckingham, B. A., Webber, M. J., Appel, E. A. 2020


    Treatment of patients with diabetes with insulin and pramlintide (an amylin analogue) is more effective than treatment with insulin only. However, because mixtures of insulin and pramlintide are unstable and have to be injected separately, amylin analogues are only used by 1.5% of people with diabetes needing rapid-acting insulin. Here, we show that the supramolecular modification of insulin and pramlintide with cucurbit[7]uril-conjugated polyethylene glycol improves the pharmacokinetics of the dual-hormone therapy and enhances postprandial glucagon suppression in diabetic pigs. The co-formulation is stable for over 100 h at 37 °C under continuous agitation, whereas commercial formulations of insulin analogues aggregate after 10 h under similar conditions. In diabetic rats, the administration of the stabilized co-formulation increased the area-of-overlap ratio of the pharmacokinetic curves of pramlintide and insulin from 0.4 ± 0.2 to 0.7 ± 0.1 (mean ± s.d.) for the separate administration of the hormones. The co-administration of supramolecularly stabilized insulin and pramlintide better mimics the endogenous kinetics of co-secreted insulin and amylin, and holds promise as a dual-hormone replacement therapy.

    View details for DOI 10.1038/s41551-020-0555-4

    View details for PubMedID 32393892

  • Autologous Transplantation of Skin-Derived Precursor Cells in a Porcine Model. Journal of pediatric surgery Thomas, A., Taylor, J. S., Huynh, N., Dubrovsky, G., Chadarevian, J., Chen, A., Baker, S., Dunn, J. C. 2019


    BACKGROUND: Hirschprung's disease is characterized by aganglionic bowel and often requires surgical resection. Cell-based therapies have been investigated as potential alternatives to restore functioning neurons. Skin-derived precursor cells (SKPs) differentiate into neural and glial cells in vitro and generate ganglion-like structures in rodents. In this report, we aimed to translate this approach into a large animal model of aganglionosis using autologous transplantation of SKPs.METHODS: Juvenile pigs underwent skin procurement from the shoulder and simultaneous chemical denervation of an isolated colonic segment. Skin cells were cultured in neuroglial-selective medium and labeled with fluorescent dye for later identification. The cultured SKPs were then injected into the aganglionic segments of colon, and the specimens were retrieved within seven days after transplantation. SKPs in vitro and in vivo were assessed with histologic samples for various immunofluorescent markers of multipotency and differentiation. SKPs from the time of harvest were compared to those at the time of injection using PCR.RESULTS: Prior to transplantation, 72% of SKPs stained positive for nestin and S100b, markers of neural and glial precursor cells of neural crest origin, respectively. Markers of differentiated neurons and gliocytes, TUJ1 and GFAP, were detected in 47% of cultured SKPs. After transplantation, SKPs were identified in both myenteric and submucosal plexuses of the treated colon. Nestin co-expression was detected in the SKPs within the aganglionic colon in vivo. Injected SKPs appeared to migrate and express early neuroglial differentiation markers.CONCLUSIONS: Autologous SKPs implanted into aganglionic bowel demonstrated immunophenotypes of neuroglial progenitors. Our results suggest that autologous SKPs may be potentially useful for cell-based therapy for patients with enteric nervous system disorders.TYPE OF STUDY: Basic science.

    View details for DOI 10.1016/j.jpedsurg.2019.09.075

    View details for PubMedID 31704043

  • Ultrasound/microbubble-mediated targeted delivery of anticancer microRNA-loaded nanoparticles to deep tissues in pigs. Journal of controlled release : official journal of the Controlled Release Society Di Ianni, T., Bose, R. J., Sukumar, U. K., Bachawal, S., Wang, H., Telichko, A., Herickhoff, C., Robinson, E., Baker, S., Vilches-Moure, J. G., Felt, S. A., Gambhir, S. S., Paulmurugan, R., Dahl, J. D. 2019


    In this study, we designed and validated a platform for ultrasound and microbubble-mediated delivery of FDA-approved pegylated poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with anticancer microRNAs (miRNAs) to deep tissues in a pig model. Small RNAs have been shown to reprogram tumor cells and sensitize them to clinically used chemotherapy. To overcome their short intravascular circulation half-life and achieve controlled and sustained release into tumor cells, anticancer miRNAs need to be encapsulated into nanocarriers. Focused ultrasound combined with gas-filled microbubbles provides a noninvasive way to improve the permeability of tumor vasculature and increase the delivery efficiency of drug-loaded particles. A single handheld, curvilinear ultrasound array was used in this study for image-guided therapy with clinical-grade SonoVue contrast agent. First, we validated the platform on phantoms to optimize the microbubble cavitation dose based on acoustic parameters, including peak negative pressure, pulse length, and pulse repetition frequency. We then tested the system in vivo by delivering PLGA nanoparticles co-loaded with antisense-miRNA-21 and antisense-miRNA-10b to pig liver and kidney. Enhanced miRNA delivery was observed (1.9- to 3.7-fold increase) as a result of the ultrasound treatment compared to untreated control regions. Additionally, we used highly fluorescent semiconducting polymer nanoparticles to visually assess nanoparticle extravasation. Fluorescent microscopy suggested the presence of nanoparticles in the extravascular compartment. Hematoxylin and eosin staining of treated tissues did not reveal tissue damage. The results presented in this manuscript suggest that the proposed platform may be used to safely and noninvasively enhance the delivery of miRNA-loaded nanoparticles to target regions in deep organs in large animal models.

    View details for DOI 10.1016/j.jconrel.2019.07.024

    View details for PubMedID 31326463

  • In Vivo Wireless Sensors for Gut Microbiome Redox Monitoring. IEEE transactions on bio-medical engineering Baltsavias, S. n., Van Treuren, W. n., Weber, M. n., Charthad, J. n., Baker, S. n., Sonnenburg, J. L., Arbabian, A. n. 2019


    A perturbed gut microbiome has recently been linked with multiple disease processes, yet researchers currently lack tools that can provide in vivo, quantitative, and real-time insight into these processes and associated host-microbe interactions. We propose an in vivo wireless implant for monitoring gastrointestinal tract redox states using oxidation-reduction potentials (ORP). The implant is powered and conveniently interrogated via ultrasonic waves. We engineer the sensor electronics, electrodes, and encapsulation materials for robustness in vivo, and integrate them into an implant that endures autoclave sterilization and measures ORP for 12 days implanted in the cecum of a live rat. The presented implant platform paves the way for long-term experimental testing of biological hypotheses, offering new opportunities for understanding gut redox pathophysiology mechanisms, and facilitating translation to disease diagnosis and treatment applications.

    View details for DOI 10.1109/TBME.2019.2948575

    View details for PubMedID 31634824

  • Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier. Nature biomedical engineering Stapleton, L. M., Steele, A. N., Wang, H. n., Lopez Hernandez, H. n., Yu, A. C., Paulsen, M. J., Smith, A. A., Roth, G. A., Thakore, A. D., Lucian, H. J., Totherow, K. P., Baker, S. W., Tada, Y. n., Farry, J. M., Eskandari, A. n., Hironaka, C. E., Jaatinen, K. J., Williams, K. M., Bergamasco, H. n., Marschel, C. n., Chadwick, B. n., Grady, F. n., Ma, M. n., Appel, E. A., Woo, Y. J. 2019; 3 (8): 611–20


    Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer-nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.

    View details for DOI 10.1038/s41551-019-0442-z

    View details for PubMedID 31391596

  • A Bird's-Eye View of Regulatory, Animal Care, and Training Considerations Regarding Avian Flight Research. Comparative medicine Baker, S. W., Tucci, E. R., Felt, S. A., Zehnder, A. n., Lentink, D. n., Vilches-Moure, J. G. 2019


    A thorough understanding of how animals fly is a central goal of many scientific disciplines. Birds are a commonly usedmodel organism for flight research. The success of this model requires studying healthy and naturally flying birds in a laboratory setting. This use of a nontraditional laboratory animal species presents unique challenges to animal care staff and researchers alike. Here we review regulatory, animal care, and training considerations associated with avian flight research.

    View details for DOI 10.30802/AALAS-CM-18-000033

    View details for PubMedID 30764892

  • A mm-Sized Wireless Implantable Device for Electrical Stimulation of Peripheral Nerves IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS Charthad, J., Chang, T., Liu, Z., Sawaby, A., Weber, M. J., Baker, S., Gore, F., Felt, S. A., Arbabian, A. 2018; 12 (2): 257–70


    A wireless electrical stimulation implant for peripheral nerves, achieving >10× improvement over state of the art in the depth/volume figure of merit, is presented. The fully integrated implant measures just 2 mm × 3 mm × 6.5 mm (39 mm3, 78 mg), and operates at a large depth of 10.5 cm in a tissue phantom. The implant is powered using ultrasound and includes a miniaturized piezoelectric receiver (piezo), an IC designed in 180 nm HV BCD process, an off-chip energy storage capacitor, and platinum stimulation electrodes. The package also includes an optional blue light-emitting diode for potential applications in optogenetic stimulation in the future. A system-level design strategy for complete operation of the implant during the charging transient of the storage capacitor, as well as a unique downlink command/data transfer protocol, is presented. The implant enables externally programmable current-controlled stimulation of peripheral nerves, with a wide range of stimulation parameters, both for electrical (22 to 5000 μA amplitude, ∼14 to 470 μs pulse-width, 0 to 60 Hz repetition rate) and optical (up to 23 mW/mm2 optical intensity) stimulation. Additionally, the implant achieves 15 V compliance voltage for chronic applications. Full integration of the implant components, end-to-end in vitro system characterizations, and results for the electrical stimulation of a sciatic nerve, demonstrate the feasibility and efficacy of the proposed stimulator for peripheral nerves.

    View details for DOI 10.1109/TBCAS.2018.2799623

    View details for Web of Science ID 000428547600001

    View details for PubMedID 29578414

  • Effect of Ex Vivo-Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques TRANSPLANTATION Duran-Struuck, R., Sondermeijer, H. P., Buhler, L., Alonso-Guallart, P., Zitsman, J., Kato, Y., Wu, A., McMurchy, A. N., Woodland, D., Griesemer, A., Martinez, M., Boskovic, S., Kawai, T., Cosimi, A., Wuu, C., Slate, A., Mapara, M. Y., Baker, S., Tokarz, R., D'Agati, V., Hammer, S., Pereira, M., Lipkin, W., Wekerle, T., Levings, M. K., Sykes, M. 2017; 101 (2): 274–83


    Infusion of recipient regulatory T (Treg) cells promotes durable mixed hematopoietic chimerism and allograft tolerance in mice receiving allogeneic bone marrow transplant (BMT) with minimal conditioning. We applied this strategy in a Cynomolgus macaque model.CD4 CD25 Treg cells that were polyclonally expanded in culture were highly suppressive in vitro and maintained high expression of FoxP3. Eight monkeys underwent nonmyeloablative conditioning and major histocompatibility complex mismatched BMT with or without Treg cell infusion. Renal transplantation (from the same BMT donor) was performed 4 months post-BMT without immunosuppression to assess for robust donor-specific tolerance.Transient mixed chimerism, without significant T cell chimerism, was achieved in the animals that received BMT without Treg cells (N = 3). In contrast, 2 of 5 recipients of Treg cell BMT that were evaluable displayed chimerism in all lineages, including T cells, for up to 335 days post-BMT. Importantly, in the animal that survived long-term, greater than 90% of donor T cells were CD45RA CD31, suggesting they were new thymic emigrants. In this animal, the delayed (to 4 months) donor kidney graft was accepted more than 294 days without immunosuppression, whereas non-Treg cell BMT recipients rejected delayed donor kidneys within 3 to 4 weeks. Early CMV reactivation and treatment was associated with early failure of chimerism, regardless of Treg cell administration.Our studies provide proof-of-principle that, in the absence of early CMV reactivation (and BM-toxic antiviral therapy), cotransplantation of host Treg cell can promote prolonged and high levels of multilineage allogeneic chimerism and robust tolerance to the donor.

    View details for DOI 10.1097/TP.0000000000001559

    View details for Web of Science ID 000393647400021

    View details for PubMedID 27846155

    View details for PubMedCentralID PMC5263090

  • Using reduced personal protective equipment in an endemically infected mouse colony. Journal of the American Association for Laboratory Animal Science : JAALAS Baker, S. W., Prestia, K. A., Karolewski, B. 2014; 53 (3): 273-7


    Personal protective equipment (PPE) frequently is used to reduce the risk of spreading adventitial diseases in rodent colonies. The PPE worn often reflects the historic practices of the research institution rather than published performance data. Standard PPE for a rodent facility typically consists of a disposable hair bonnet, gown, face mask, shoe covers, and gloves, which are donned on facility entry and removed on exiting. This study evaluated the effect of a reduced PPE protocol on disease spread within an endemically infected mouse colony. In the reduced protocol, only the parts of the wearer that came in direct contact with the mice or their environment were covered with PPE. To test the reduced PPE protocol, proven naïve mice were housed in a facility endemically infected with murine norovirus and mouse hepatitis virus for 12 wk. During that time, routine husbandry operations were conducted by using either the standard or reduced PPE protocols. All study mice remained free of virus antibody when reduced PPE was implemented. These results indicate that reduced PPE is adequate for disease containment when correct techniques for handling microisolation caging are used. Reducing the amount of PPE used in an animal facility affords considerable cost savings yet limits the risk of disease spread.

    View details for PubMedID 24827569

    View details for PubMedCentralID PMC4128565

  • Temporal lobe epilepsy in a cat with a pyriform lobe oligodendroglioma and hippocampal necrosis JOURNAL OF FELINE MEDICINE AND SURGERY Vanhaesebrouck, A. E., Posch, B., Baker, S., Plessas, I. N., Palmer, A. C., Constantino-Casas, F. 2012; 14 (12): 932–37


    A 14-year-old male domestic shorthair cat presented with an acute onset of aggressive behaviour, fear and hypersalivation. Neurological examination revealed bilateral mydriasis and left-sided facial twitching and hemiparesis. Magnetic resonance imaging (MRI) showed moderate bilateral symmetrical T2-hyperintensity along the entire hippocampus and bilateral asymmetric T2-hyperintensity in the pyriform lobes. Marked bilateral contrast enhancement of the hippocampus was evident on post-contrast T1-weighted images. The partial complex seizures were refractory to medical treatment and the cat was euthanased 4 days after admission. The clinical and MRI findings were consistent with feline hippocampal necrosis (FHN). On histopathology, neuronal necrosis and astrocytosis were present in the hippocampi and pyriform lobes. In addition, an oligodendroglioma was detected in the right pyriform lobe. Contrary to previous reports of FHN in which no underlying cause could be identified, we believe that in this case the seizure focus arose from a neoplastic lesion within the right pyriform lobe. This unique case report represents the so-called 'dual pathology' of temporal lobe epilepsy in humans, in which an extrahippocampal lesion within the temporal lobe results in hippocampal sclerosis.

    View details for DOI 10.1177/1098612X12454419

    View details for Web of Science ID 000312556600020

    View details for PubMedID 22791561