Biomedical Research Core Facilities
Fall 2020 Newsletter
The Perelman School of Medicine is proud to support our integral research core facilities and research teams. Please stay safe and be well!
In this issue:

  • Virtual Cores Day - September 24th, 2020
  • Core Facilities Spotlight
  • Chemical and Nanoparticle Synthesis Core Facility
  • Comparative Pathology Core Facility - Penn Vet
  • Human Immunology Core Facility
  • OCRC Tumor BioTrust
Virtual Cores Day - September 24th, 2020
We are delighted to report that ~60 core facilities across CHOP, Penn, and Wistar participated in the first ever virtual version of this event, attended by more than 300 people.

While we hope circumstances permit return to an in-person event next year, in the meantime we encourage you to visit the link below for a full index of PSOM Cores Day video presentations.

The Penn Chemical and Nanoparticle Synthesis Core (CNSC) is excited to announce the availability of Site-Specific Antibody Labeling Services. The CNSC is offering a service to conjugate customer-provided antibodies with a wide range of labels, including biotin, fluorescent dyes, and oligonucleotides. Site-specific antibody labeling ensures no interference with antibody binding and can improve the performance of immunoassays. The benefits of site-specifically labeled antibodies are enabled by the conjugation technology developed by AlphaThera. Read more about the technology here: https://alphathera.com/why-sitespecific.

Some applications supported by our antibody labeling service include:

  • ELISA: SIte-specifically label your antibodies with Biotin and achieve ELISA that is up to 10x more sensitive. For Direct or Sandwich ELISA.
  • Click-Chemistry: Label your antibodies with Azide or DBCO for copper-free click chemistry.
  • Nanoparticle / Surface Immobilization: Assure homogeneous surface immobilization and orientation of your antibodies on surfaces, including gold surfaces with Thiol-Antibody conjugations. Also support His-tag and GST-tag conjugations.
  • CUT&RUN (Improved ChiP-Seq): Covalently conjugate MNase directly to antibodies and use for the CUT&RUN assay or other cell digestion assays. Epigenetic mapping is vastly improved with oYo-Link MNase. Low cell counts yield high DNA enrichment results
  • Single-Cell / iPCR with DNA-Antibody Conjugates: Site-specifically attach Oligonucleotides to your antibodies for various applications. Our conjugations support ss and ds Oligos ranging from 20-80 base pairs.

Reach out to the CNSC core for more information and questions about antibody compatibility, pricing, and orders. We look forward to serving your antibody conjugation needs.

Penn Vet’s Comparative Pathology Core (CPC) offers state-of-the-art pathology services to enhance the important biomedical research on campus. Our immunohistochemistry service utilizes an automated staining platform (Leica BOND RXm) for chromogenic IHC, immunofluorescence or in situ hybridization on paraffin-embedded or frozen tissue sections and cytological preparations. The CPC has numerous in-stock optimized antibodies for mouse and other animal tissues, as well as the ability to work-up novel antibodies for investigators. Recently, pathologists in the CPC assisted Dr. Nicola Mason by determining the IHC binding profile of two novel antibodies, using a custom built tissue microarray for the high-throughput screening of normal and target tissues (Haran KP et al. Generation and Validation of an Antibody to Canine CD19 for Diagnostic and Future Therapeutic Purposes. Vet Pathol. 2020 Mar;57(2):241-252. doi: 10.1177/0300985819900352. PMID: 32081102; PMCID: PMC7462180). 
 
Investigators can utilize the CPC Complete Pathologic Assessment for comprehensive animal model examinations, including autopsies (with gross pathology and organ weight) and histopathological examination of genetically engineered or test article-treated mice and matched controls. For example, The CPC provides thorough pathological investigations of animal models to help interpret efficacy and potential on- or off-target toxicities of specific CAR-T cell products and help to provide preclinical data to guide clinical trial design (Lee J, Lundgren DK, Mao X, Manfredo-Vieira S, Nunez-Cruz S, Williams EF, Assenmacher CA, Radaelli E, Oh S, Wang B, Ellebrecht CT, Fraietta JA, Milone MC, Payne AS. Antigen-specific B-cell depletion for precision therapy of mucosal pemphigus vulgaris. J Clin Invest. 2020 Aug 20:138416. doi: 10.1172/JCI138416. PMID: 32817591).
 
The CPC also offers the Aperio digital platform to provide brightfield and fluorescence whole slide digital scanning of fixed tissues. This is configured with a server and sophisticated database management system for central storage, analysis, and sharing. The system is fully integrated with whole slide imaging software for advanced automated quantitative analysis of subcellular structures, cells, and tissues, and has the capability to perform a range of analyses, including individual cell or area quantification, and pattern recognition. A recent study in which the CPC quantified the level of expression of a specific protein in the substantia nigra of mice highlights the effectiveness of this modality. (Chattopadhyay M, Chowdhury AR, Feng T, Assenmacher CA, Radaelli E, Guengerich FP, Avadhani NG. Mitochondrially targeted cytochrome P450 2D6 is involved in monomethylamine-induced neuronal damage in mouse models. J Biol Chem. 2019 Jun 28;294(26):10336-10348. doi: 10.1074/jbc.RA119.008848. PMID: 31113867; PMCID: PMC6664168)
Core Facilities Spotlight: Human Immunology Core Facility
Suspension of all but COVID-19-related research was anything but a quiet time for the Human Immunology Core as investigators pivoted their research programs in response to the pandemic. We began with development of workflows and SOPs for safe handling of COVID-19 samples at a time when the extent and kinetics of viremia were not yet understood. In close collaboration with EHRS, the HIC technical director, Ling Zhao, and senior research investigator, Jean Scholz, together with Nina Luning Prak, the HIC scientific director, developed and implemented BSL2-enhanced procedures for all COVID-related blood processing work.  Members of the HIC staff, Hongen Wang, Yangzhu Du, Zhenyu Huang, Racheli Ben Shimol and Xiaomei Liu processed over 140 high-volume and high complexity samples from COVID-19 patients -- some of which were included in a recent high-profile publication by Penn investigators (Ref. 1). As part of this ongoing effort, the HIC worked closely with the COVID-Processing Unit, which also received help from Jim Riley, HIC faculty. During the shut-down, the HIC also worked with Ned Haubein, Kaitlyn Phelan and the rest of the LabVantage team on new data entry templates and procedures for COVID and other clinical trial sample processing.

The HIC is continuing to process samples from COVID patients and is working with the Penn BioBank to coordinate processing of selected samples for viable cell cryopreservation in ongoing research studies. During the shut-down, the HIC also provided cryopreserved peripheral blood mononuclear cells to investigators for their COVID research.

In addition to sample processing work, the HIC also performed immune receptor repertoire sequencing studies on COVID-19 patients and has generated extensive data sets of both BCR and TCR sequences from patients with a range of different disease phenotypes. HIC staff members Wenzhao Meng, Fang Liu, Zheng Cui, and Aaron Rosenfeld have contributed data and data analysis expertise to a recent publication on COVID-19 by Penn investigators, including HIC scientific director Nina Luning Prak (Ref. 2). Meng, Rosenfeld and Luning Prak also co-authored a preview piece entitled “Mining the Antibody Repertoire for Solutions to SARS-CoV-2,” published earlier this month (Ref. 3). Dr. Luning Prak, who also serves as the Chair of the Adaptive Immune Receptor Repertoire (AIRR) Community, co-chaired a 3-day virtual conference on immune repertoire profiling studies and data sharing (“Leveraging Adaptive Immune Receptor Repertoire Sequencing Data to Inform the Biology of COVID-19,” for further details please see https://www.antibodysociety.org/the-airr-community/meetings/airr-community-special-event-response-to-covid-19/).

The HIC has also been hard at work on cellular immunoassays during the pandemic and has established a partnership with LifeSensors, a PA-based company with expertise in antigen manufacturing. Antigens produced by LifeSensors and other vendors are being used in flow cytometry-based assays and for sorts for immune repertoire profiling and other studies. In the Hospital of the University of Pennsylvania, Nina Luning Prak, Ping Wang and Dan Herman have been evaluating and establishing SARS-CoV-2 serology assays in the clinical lab. With the help of Dave Allman, Carly Roman and Scott Hensley, HUP Clinical Immunology Lab staff members Joyce Gonzalez, Andy Gaano and Erin Henry have adapted a research assay for the detection of IgG and IgA antibodies to the SARS-CoV-2 receptor binding domain (RBD) to run on automated instruments in the clinical lab. The Hensley lab provided reagents and starting protocols for the assay and manufactured a large quantity of RBD antigen for the clinical lab. The HIC and the HUP clinical labs have worked together closely for the past several months to evaluate and perform over 14 different assay kits/types for SARS-CoV-2 antibody detection including lateral flow assay, ELISA, chemiluminescence, flow cytometry and addressable bead formats.

In sum, the HIC has access to and expertise in a wide range of cellular and molecular assays for SARS-CoV-2 and is actively involved in many different COVID-19 research efforts on the Penn campus.

References:
1. Mathew, D. et al. (2020) “Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications.” Science. Vol. 369(6508): eabc8511.
2. Kuri-Cervantes, L. et al. (2020) “Comprehensive mapping of immune perturbations associated with severe COVID-19,” Science Immunol. Vol. 5(49): eabd7114.
3. Meng, W. et al. (2020) “Mining the antibody repertoire for solutions to SARS-CoV-2,” Cell Host Microbe. Vol. 28(4): 499-501.
Core Facilities Spotlight: OCRC Tumor BioTrust Collection
The Ovarian Cancer Research Center Tumor BioTrust Collection is open and continues to collect fresh cancer tissue specimens, as well as plasma, serum, peripheral blood mononuclear cells (PBMC), blood and other biological samples from all cases of ovarian cancer patients. We handle collection, processing, storage, and distribution of primary and recurrent ovarian tumor samples as well as blood. We also house formalin fixed paraffin embedded (FFPE) samples. Samples collected through the Penn Legacy Tissue Program (PLTP) (e.g. rapid autopsy) are also available and a quote can be provided upon request. We will also work with investigators to prospectively collect specific samples to support their research within Penn research community as well as in outside institutions and bio-tech/bio-pharma companies. In order to protect our users and staff, we have implemented ‘no contact’ sample pick-ups and drop-offs.

We are offering the following sample types:

  • Fresh Tumor Tissue
  • Frozen Tumor Tissue
  • Enzyme Digested Tumor Cells
  • Serum
  • Plasma
  • Peripheral Blood Mononuclear Cells (PBMC)
  • OCT
  • Formalin Fixed Paraffin Embedded (FFPE)
  • Tissue Microarray (TMA)
  • Samples from rapid autopsies

More info about the core and pricing can be found at:

Representative Publications:
 
An autologous humanized patient-derived-xenograft platform to evaluate immunotherapy in ovarian cancer
Sarah B. Gitto, Hyoung Kim, Stavros Rafail, Dalia K. Omran, Sergey Medvedev, Yasuto Kinose, Alba Rodriguez-Garcia, Ahron J. Flowers, Haineng Xu, Lauren E. Schwartz, Daniel J. Powell Jr., Fiona Simpkins
Gynecologic Oncology 156 (2020) 222e232.

CAR T Cells Targeting MISIIR for the Treatment of Ovarian Cancer and Other Gynecologic Malignancies
Alba Rodriguez-Garcia, Prannda Sharma, Mathilde Poussin, Alina C. Boesteanu, Nicholas G. Minutolo, Sarah B. Gitto, Dalia K. Omran, Matthew K. Robinson, Gregory P. Adams, Fiona Simpkins, and Daniel J. Powell, Jr.
Molecular Therapy (2019), https://doi.org/10.1016/j.ymthe.2019.11.028.

Imaging Collagen Alterations in STICs and High Grade Ovarian Cancers in the Fallopian Tubes by Second Harmonic Generation Microscopy
Eric C. Rentchler, Kristal L. Gant, Ronny Drapkin, Manish Patankar and Paul J. Campagnola,*
Cancers 2019, 11, 1805; doi:10.3390/cancers11111805.

CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary
Shoumei Bai, Wanhong Zhu, Lan Coffman, Anda Vlad, Lauren E. Schwartz, Esther Elishaev, Ronny Drapkin and Ronald J Buckanovich
Cancers 2019, 11, 1710; doi:10.3390/cancers11111710.

Innervation of cervical carcinoma is mediated by cancer-derived exosomes
Christopher T. Lucido, Emily Wynja, Marianna Madeoa, Caitlin S.Williamson, Lauren E. Schwartz, Brittney A. Imblumc, Ronny Drapkin, Paola D. Vermeer
Gynecol Oncol. 2019 Jul;154(1):228-235.
Contact Us
Ovarian Cancer Research Center Tumor BioTrust Collection
Ehay Jung, Technical Director
Smilow CTR 08-191A
3400 Civic Center Blvd
Philadelphia, PA 19104
Phone: 215-746-5137
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