In this issue:



• Announcements
• ABRF Annual Meeting - April 21-24, 2024
• Cores Day Save-the-Date: September 25, 2024
• Core Resource Funding Opportunity
• Core Facilities Spotlight
• Human Immunology Core Facility
• Molecular Pathology & Imaging Core Facility
• OCRC Tumor BioTrust Collection
• Rodent Cardiovascular Phenotyping Core
• Tumor Tissue / Biospecimen Bank

Announcements: ABRF Annual Meeting: April 21-24, 2024

The Association of Biomolecular Resources Facilities (ABRF) Annual Meeting is an international program that provides timely updates on cutting-edge science and its execution in a shared resource/core facility setting. These meetings also offer informative and practical workshops as well as ample networking opportunities with academics, corporate, and technology partner colleagues.  This year's meeting will be held from April 21-24 in Minneapolis, Minnesota and ABRF members receive a discount when registering. Please click here for more information.

If you are not yet a member, we encourage you to visit the ABRF website , and to contact April Weakley (aweakley@pennmedicine.upenn.edu) if you would like to join the organization at no charge to you via PSOM’s institutional membership. 

Announcements: Cores Day Save-the-Date: September 25, 2024

We are delighted to announce Cores Day 2024! Please mark your calendars for Wednesday, September 25, 2024 from 10am-3pm.

We are excited to be once again be holding the event in the Smilow lobby. To accommodate as many interested facilities as possible, the event will be split into AM (10-12) and PM (1-3) shifts, with participating core facilities rotating out around lunchtime.

The annual Cores Day event is a joint venture with CHOP, PSOM, Penn Vet, and Wistar in an effort to showcase the many outstanding biomedical research resources and services available throughout our campus. This event is an opportunity for students, faculty, and staff to interface with a multitude of research core facilities via informational tables staffed by core facility personnel.  

Stay tuned for more details, and we hope to see you on Wednesday, September 25! 

Announcements: Core Resource Funding Opportunity

We are pleased to announce the Core Facility Strategic Funding Initiative has been renamed the "Core Resource Funding Opportunity" to better reflect the goals and scope of the initiative.

This funding approach is specifically designed to foster investment in support of our vital research core facility community.

Please note that despite the updated name, all requirements, as well as the request submission process will remain exactly the same. This change will not affect any ongoing projects or proposals.

• Funds may be used for a variety of purposes, such as new equipment, educational outreach, research/development, and more.  
• Core facilities are free to apply for funding as needs are identified, and applications will be accepted on a rolling basis.
• There is no specific limit to the amount of funds a core facility may request; support will be based on justification, strategic need, and committed partnerships.

Please note that core facilities are encouraged to seek other funding partners (ex. Departments, Centers, Institutes) prior to submitting a request.

To submit a request for supplemental funding, please click here:

https://www.med.upenn.edu/cores/core-resource-funding-opportunity.html

Warmest congratulations to the Cell & Developmental Biology Microscopy Core Facility, who recently received funding through this opportunity.

Please contact April Weakley (aweakley@pennmedicine.upenn.edu) with any questions or concerns.

Core Facilities Spotlight: Human Immunology Core Facility - RRID:SCR_022380

Contributed by Jean L. Scholz, PhD

It’s full speed ahead for the HIC as we continue to support clinical studies and other projects across the local research community. In 2023 we created a new website (Fig. 1), with help from the PMACS MODX Web Team plus extensive input from all HIC staff and Path BioResource (PBR).

The PBR team continues to assist with account and project setup for clients, billing, and other financial services. The HIC also bills some of its projects through iLab. 

The HIC’s cellular immunoassay services continue to be heavily used. Some recent projects have taken advantage of our new Luminex FLEXMAP 3D high-throughput multiplexing instrument (the core now has two of these instruments, one of which is pictured in Fig. 2).

With investigators in the Department of Obstetrics and Gynecology, the HIC developed novel methods to cryopreserve and immunophenotype red blood cells (RBCs), including the development of an 11-color red blood cell immunophenotyping panel. These methods were used in a recent JAMA publication (ref. 1) which showed that fetal RBCs are present at very low levels in early pregnancy and abortion, indicating that therapy and testing with Rh immune globulin is not needed. This publication received a top 20 clinical research achievement award for 2023 from the Clinical Research Forum. 

The HIC’s molecular lab remains busy with investigators using our in-house BCR/TCR sequencing platforms and data analysis services, exemplified by recent collaborative work (Fig. 3). In this study (ref. 2), B cell clonal networks were analyzed in the lungs and lung lymph nodes of young organ donors. B cell clonal expansion and somatic hypermutation including bronchus associated lymphoid-like structures were found in lungs of young donors and receded with age.

The HIC is also actively working on in-house single cell analysis pipelines for paired IgH/IgL and TCR data. If you have any questions about new immunology technologies, cell products or assays for your research, please contact us or visit us online.

References

(1)  Horvath S, Huang Z, Koelper NC, Martinez C, Tsao PY, Zhao L, Goldberg AB, Hannum C, Putt ME, Luning Prak ET, Schreiber CA. Induced Abortion and the Risk of Rh Sensitization. JAMA 2023 Sep 26;330(12):1167-1174. doi: 10.1001/jama.2023.16953.

(2)  Matsumoto R, Gray J, Rybkina K, Oppenheimer H, Levy L, Friedman LM, Khamaisi M, Meng W, Rosenfeld AM, Guyer RS, Bradley MC, Chen D, Atkinson MA, Brusko TM, Brusko M, Connors TJ, Luning Prak ET, Hershberg U, Sims PA, Hertz T, Farber DL. Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity. Nat Immunol. 2023 Aug; 24(8):1370-1381. doi: 10.1038/s41590-023-01557-3.

Core Facilities Spotlight: Molecular Pathology & Imaging Core Facility - RRID:SCR_022420

The Xenium from 10x Genomics is the newest addition to the Molecular Pathology and Imaging Core.  The Xenium allows you to observe subcellular spatial gene expression of tissues with upcoming 5,000 plex panels. The Xenium is available for self-service, with a total of 4 hours of simple hands-on time spread out over 2 days. MPIC provides all equipment and reagents not provided in the 10x Genomics kits, allowing researchers to perform spatial biology on their samples at their earliest convenience and for an affordable price.  Contact MPIC’s Technical Director, Kate Bennett, at bennk@upenn.edu for pricing and scheduling information if you’re interested in utilizing this exciting piece of equipment.

Additionally, MPIC will be hosting a Visium HD Launch Party alongside 10x Genomics on March 26th.  Attendees running their samples with MPIC can expect updates and discounts on both Xenium and Visium HD products. Stay tuned for details!

Core Facilities Spotlight: OCRC Tumor BioTrust Collection - RRID:SCR_022387

Representative Publications:

Performance of computational algorithms to deconvolve heterogeneous bulk ovarian tumor tissue depends on experimental factors.

Hippen, A.A., Omran, D.K., Weber, L.M. et al. Performance of computational algorithms to deconvolve heterogeneous bulk ovarian tumor tissue depends on experimental factors. Genome Biol 24, 239 (2023). https://doi.org/10.1186/s13059-023-03077-7

Functional neuronal circuits promote disease progression in cancer.

Restaino AC, Walz A, Vermeer SJ, Barr J, Kovács A, Fettig RR, Vermeer DW, Reavis H, Williamson CS, Lucido CT, Eichwald T, Omran DK, Jung E, Schwartz LE, Bell M, Muirhead DM, Hooper JE, Spanos WC, Drapkin R, Talbot S, Vermeer PD.

Science Advances 2023 May 10;9(19):eade4443. doi: 10.1126/sciadv.ade4443.

Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker.

Taylor MS, Connie W, Fridy PC, Zhang SJ, Senussi Y, Wolters JC, Cheng WC, Heaps J, Miller BD, Mori K, Cohen L, Jiang H, Molloy KR, Norden BL, Chait BT, Goggins M, Bhan I, Franses JW, Yang X, Taplin ME, Wang X, Christiani DC, Johnson BE, Meyerson M, Uppaluri R, Egloff AM, Denault EN, Spring LM, Wang TL, Shih IM, Jung E, Arora KS, Zukerberg LR, Yilmaz OH, Chi G, Matulonis UA, Song Y, Nieman L, Parikh AR, Strickland M, Corcoran RB, Mustelin T, Eng G, Yilmaz ÃH, Skates SJ, Rueda BR, Drapkin R, Klempner SJ, Deshpande V, Ting DT, Rout MP, LaCava J, Walt DR, Burns KH.

BioRxiv 2023 Mar 17:2023.01.25.525462. doi: 10.1101/2023.01.25.525462. Preprint

Folate Receptor Beta as a Direct and Indirect Target for Antibody-Based Cancer Immunotherapy

Allison G. Roy, J. Michael Robinson, Prannda Sharma, Alba Rodriguez-Garcia, Mathilde A. Poussin, Cheryl Nickerson-Nutter, and Daniel J. Powell, Jr.

https://pubmed.ncbi.nlm.nih.gov/34070369

Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma.

Barr JL, Kruse A, Restaino AC, Tulina N, Stuckelberger S, Vermeer SJ, Williamson CS, Vermeer DW, Madeo M, Stamp J, Bell M, Morgan M, Yoon J-Y, Mitchell MA, Budina A, Omran DK, Schwartz LE, Drapkin R, Vermeer PD. Cells. 2021; 10(12):3491.

https://doi.org/10.3390/cells10123491

Systematic analysis of CD39, CD103, CD137, and PD-1 as biomarkers for naturally occurring tumor antigen-specific TILs.

Eiva MA, Omran DK, Chacon JA, Powell DJ Jr.

Eur J Immunol. 2021 Sep 10. doi: 10.1002/eji.202149329. Epub ahead of print.

https://pubmed.ncbi.nlm.nih.gov/34505280/

CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy.

Rodriguez-Garcia A, Lynn RC, Poussin M, Eiva MA, Shaw LC, O'Connor RS, Minutolo NG, Casado-Medrano V, Lopez G, Matsuyama T, Powell DJ Jr.

Nat Commun. 2021 Feb 9;12(1):877. doi: 10.1038/s41467-021-20893-2.

https://pubmed.ncbi.nlm.nih.gov/33563975/

Inhibition of relaxin autocrine signaling confers therapeutic vulnerability in ovarian cancer.

Burston HE, Kent OA, Communal L, Udaskin ML, Sun RX, Brown KR, Jung E, Francis KE, La Rose J, Lowitz JK, Drapkin R, Mes-Masson AM, Rottapel R.

J Clin Invest. 2021 Feb 9:142677. doi: 10.1172/JCI142677.

https://pubmed.ncbi.nlm.nih.gov/33561012/

Combining PARP with ATR inhibition overcomes PARP inhibitor and platinum resistance in ovarian cancer models.

Kim H, Xu H, George E, Hallberg D, Kumar S, Jagannathan V, Medvedev S, Kinose Y, Devins K, Verma P, Ly K, Wang Y, Greenberg RA, Schwartz L, Johnson N, Scharpf RB, Mills GB, Zhang R, Velculescu VE, Brown EJ, Simpkins F.

Nat Commun. 2020 Jul 24;11(1):3726. doi: 10.1038/s41467-020-17127-2.

https://pubmed.ncbi.nlm.nih.gov/32709856/

PARP Theranostic Auger Emitters Are Cytotoxic in BRCA Mutant Ovarian Cancer and Viable Tumors from Ovarian Cancer Patients Enable Ex-Vivo Screening of Tumor Response. Molecules.

Riad A, Gitto SB, Lee H, Winters HD, Martorano PM, Hsieh CJ, Xu K, Omran DK, Powell DJ Jr, Mach RH, Makvandi M.

2020 Dec 19;25(24):6029. doi: 10.3390/molecules25246029.

https://pubmed.ncbi.nlm.nih.gov/33352773/

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.

Core Facilities Spotlight: Rodent Cardiovascular Phenotyping Core - RRID:SCR_022419

Recent publications:

RIP140 deficiency enhances cardiac fuel metabolism and protects mice from heart failure.

Yamamoto T, Maurya SK, Pruzinsky E, Batmanov K, Xiao Y, Sulon SM, Sakamoto T, Wang Y, Lai L, McDaid KS, Shewale SV, Leone TC, Koves TR, Muoio DM, Dierickx P, Lazar MA, Lewandowski ED, Kelly DP.

J Clin Invest. 2023 May 1;133(9):e162309. doi: 10.1172/JCI162309.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145947/

mTORC1 Inhibitor Rapamycin Inhibits Growth of Cerebral Cavernous Malformation in Adult Mice.

Li L, Ren AA, Gao S, Su YS, Yang J, Bockman J, Mericko-Ishizuka P, Griffin J, Shenkar R, Alcazar R, Moore T, Lightle R, DeBiasse D, Awad IA, Marchuk DA, Kahn ML, Burkhardt JK.

Stroke. 2023 Nov;54(11):2906-2917. doi: 10.1161/STROKEAHA.123.044108.

https://www.ahajournals.org/doi/10.1161/STROKEAHA.123.044108

Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation.

Kim B, Zhao W, Tang SY, Levin MG, Ibrahim A, Yang Y, Roberts E, Lai L, Li J, Assoian RK, FitzGerald GA, Arany Z.

J Clin Invest. 2023 Dec 15;133(24):e173160. doi: 10.1172/JCI173160.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10721151/

Core Facilities Spotlight: Tumor Tissue / Biospecimen Bank - RRID:SCR_022430 

Expansion of Tumor Tissue and Biospecimen Bank (TTAB) Tissue Collection Services at Penn Presbyterian Medical Center (PPMC)

Dear Investigators,

We hope this message finds you well and thriving in your important research endeavors. We are excited to share news that significantly broadens the scope and potential of your research projects. Recognizing the challenges and constraints of sourcing high-quality biological specimens, we are delighted to announce a major expansion of our tissue collection services at the Penn Presbyterian Medical Center (PPMC). This development is a key milestone in our commitment to providing you with access to a broader and more diverse range of tissue samples, critical for the success of your research.

What This Means for Your Research:

• Broader Access: This expansion grants you access to an increased variety of tissue types and pathologies, broadening the diversity and reach of your research.
• Efficient Collection Process: In close collaboration with the PPMC Pathology Department, we have ensured that the collection process is streamlined, ethical, and fully compliant with all regulatory standards, guaranteeing you access to the highest quality specimens.
• New Collaborative Possibilities: The expansion fosters new opportunities for multidisciplinary collaborations and research initiatives with clinicians and researchers at PPMC.

Getting Started with Collections at PPMC:

To begin utilizing tissue collection services at PPMC, please follow these steps:

• Contact Us: Reach out to our team at [valdivie@pennmedicine.upenn.edu | anupma.nayak@pennmedicine.upenn.edu] to express your interest and discuss your specific tissue collection needs.
• Project Approval: Submit a brief overview of your research project for approval, ensuring alignment with our collection capabilities and ethical guidelines.
• Collection Coordination: Once approved, our team will coordinate with you to facilitate the collection process according to your project timeline and specifications.

We are dedicated to supporting your research endeavors every step of the way and aim to make this expansion as beneficial and straightforward as possible. For any inquiries or further details, please feel free to reach out to us directly.

Sincerely,

Federico Valdivieso

Technical Director

Tumor Tissue and Biospecimen Bank (TTAB)

Perelman School of Medicine

University of Pennsylvania

valdivie@pennmedicine.upenn.edu

Anupma Nayak, MBBS, MD

Associate Professor of Pathology

Director, Tumor Tissue and Biospecimen Bank (TTAB)

Perelman School of Medicine

University of Pennsylvania

Anupma.nayak@pennmedicine.upenn.edu

P.S. We welcome any feedback or suggestions you may have about this new service offering. Your input is invaluable as we strive to meet and exceed the needs of our research community.

Have you used any core products, services or facilities?

We encourage you to complete a survey to provide us feedback on your experience.

Copyright © 2024 PSOM Biomedical Research Core Facilities, All rights reserved.