In this issue:



• Announcements
• Updated Core Facilities Finder & Video Presentations
• NIH Data Management & Sharing Policy
• Core Facility Strategic Funding Initiative
• Upcoming Events
• 12/6/23 - Center for Targeted Therapeutics & Translational Nanomedicine (CT3N) Symposium
• 2024 Mouse Pathology Workshop Hosted by Comparative Pathology Core Facility - Penn Vet
• Core Facilities Spotlight
• Extracellular Vesicle Core Facility - Penn Vet
• Comparative Pathology Core Facility - Penn Vet
• OCRC Tumor BioTrust Collection

Announcements: Updated Core Facilities Finder & Video Presentations

We’re pleased to announce the recently refreshed content on the Core Facilities Finder webpage. The website is designed to be a go-to resource for both core facility directors and potential customers. In conjunction with this refresh, we encourage you to explore the available core facility presentations. These videos are not just a snapshot in time, but can also serve as an enduring resource you may wish to share with interested users. Please contact April Weakley (aweakley@pennmedicine.upenn.edu) if you would like to provide updates or additional content. 

Announcements: NIH Data Management & Sharing Policy

In an effort to promote and share scientific data, the NIH has established a Data Management and Sharing Policy (DMSP), beginning January 25th, 2023, requiring ALL grant or renewals that generate Scientific Data to include a robust and detailed plan for how you will manage and share data during the entire funded period.

Please click here to visit PSOM's NIH Data Management & Sharing Policy website for

tips, tricks, and comprehensive support resources.

We are pleased to share our new funding approach, specifically designed to foster strategic investment in support of our vital research core facility community.

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

https://hosting.med.upenn.edu/forms/evdresearch/view.php?id=14757

• Funds may be used for a variety of strategic purposes, such as new equipment, educational outreach, research/development, and more.  
• Core facilities are free to apply for funding as strategic 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 your request.

Warmest congratulations to recent award recipients the Neurobehavior Testing Core Facility, and the Comparative Pathology Core Facility at Penn Vet, whose dedication to furthering PSOM’s strategic and scientific mission is truly inspiring.

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

Upcoming Events - 12/6/23 Center for Targeted Therapeutics & Translational Nanomedicine (CT3N) Symposium

The 2023 CT3N Symposium again features outstanding speakers from the fields of targeted therapeutics, drug delivery, biomaterials, and nanomedicine. This will be a hybrid event.

Please click here for the agenda and here for the event poster.

Penn cores facilities/centers and CT3N Corporate Members will be given the opportunity to advertise their services, offerings, and other information of interest to symposium participants during the Annual CT3N Symposium. Information of interest may include job openings, description of the ‘areas of interest’, company resources and collaboration opportunities, etc. Sales of any kind are prohibited during the symposium.

For inquires or interest please contact Jackie Rhodes jarhodes@upenn.edu.

Upcoming Events - 2024 Mouse Pathology Workshop Hosted by Comparative Pathology Core Facility - Penn Vet

Hosted by the Comparative Pathology Core Facility at Penn Vet, this hybrid workshop is designed to provide researchers working on mouse models of disease with conceptual and practical skills to optimize experimental planning of pathology endpoints and improve validity and reproducibility of results.

Beginning on January 19, 2024, the workshop will take place over 4 weeks with a mixture of asynchronous/synchronous lectures and in-person labs. Labs will take place each Friday for 3 hours. This workshop will have approximately 25 hours of work including lecture, labs & assignments.

Trainees are expected to develop practical skills and acquire proficiency in the proper collection and preparation of tissue samples for pathological assessment, as well as learning basic principles for histological interpretation of disease processes and application of digital image analysis. Trainees are also expected to become familiar with the available resources and basic scientific concepts for reliable planning and implementation of pathology endpoints to experimental mouse models of disease.

Please click here to learn more.

Core Facilities Spotlight: Extracellular Vesicle Core Facility: Penn Vet - RRID:SCR_022444

The NanoFCM, a particle analyzer of the latest generation, is available for use. A state-of-the-art flow cytometer with 3 lasers, superior optics, and low-noise electronics, this instrument detects and analyzes functional nanoparticles (40-1000 nm) at the single particle level. By analyzing ultralow scattered light from single nanoparticles, it provides high-resolution size distributions comparable to electron microscopy in 1-2 minutes.

Furthermore, it is possible to simultaneously measure multiple parameters within a sample, including a variety of surface proteins, nucleic acids, and lipids. The NanoFCM will be available for self-service, allowing researchers to perform particle count, sizing and phenotyping and troubleshooting.

Please contact Core Facility Director, Dr. Luca Musante, at musante@upenn.edu for pricing and scheduling information.

Core Facilities Spotlight: Comparative Pathology Core Facility: Penn Vet - RRID:SCR_022438

The CPC received funding through the Core Facility Strategic Funding Initiative and the Penn Vet Institute for Infectious and Zoonotic Diseases for the hiring of a new pathology fellow.

The CPC was able to purchase an additional Leica Bond RXm instrument through a Core grant opportunity from the Penn Vet Institute for Infectious and Zoonotic Diseases and internal funding from the Department of Pathobiology. This additional instrument allowed us to dramatically decrease our turnaround times for the IHC and ISH services.

The CPC will also be hosting a new edition of the Mouse Pathology Workshop, detailed in the "Events" section of this newsletter. The workshop is intended for graduate and post-doctoral students, research specialists and lab technicians, or any scientists working with mice and needing a refresher on mouse macro- and microanatomy, basic dissection and trimming skills, major disease processes, and introduction to digital pathology and image analysis, among other topics.

Publications:

Primary research at the CPC leading to publications in the last 12 months:

Assenmacher CA, Lanza M, Tarrant JC, Gardiner KL, Blankemeyer E, Radaelli E. Post Mortem Study on the Effects of Routine Handling and Manipulation of Laboratory Mice. Animals (Basel). 2022 Nov 22;12(23):3234.

Finesso G, Willis E, Tarrant JC, Lanza M, Sprengers J, Verrelle J, Banerjee E, Hermans E, Assenmacher CA, Radaelli E. Spontaneous early-onset neurodegeneration in the brainstem and spinal cord of NSG, NOG, and NXG mice. Vet Pathol. 2023 May;60(3):374-383.

Radaelli E, Assenmacher CA, Verrelle J, Banerjee E, Manero F, Khiati S, Girona A, Lopez-Lluch G, Navas P, Spinazzi M. Mitochondrial defects caused by PARL deficiency lead to arrested spermatogenesis and ferroptosis. Elife. 2023 Jul 28;12:e84710.

Collaborative research project leading to publications:

- McBrearty N, Cho C, Chen J, Zahedi F, Peck AR, Radaelli E, Assenmacher CA, Pavlak C, Devine A, Yu P, Lu Z, Zhang H, Li J, Pitarresi JR, Astsaturov I, Cukierman E, Rustgi AK, Stanger BZ, Rui H, Fuchs SY. Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells. Mol Cancer Res. 2023 Mar 1;21(3):228-239.

Sorobetea D, Matsuda R, Peterson ST, Grayczyk JP, Rao I, Krespan E, Lanza M, Assenmacher CA, Mack M, Beiting DP, Radaelli E, Brodsky IE. Inflammatory monocytes promote granuloma control of Yersinia infection. Nat Microbiol. 2023 Apr;8(4):666-678.

- Liu J, Cheng L, El-Mekkoussi H, Assenmacher CA, Lee MYY, Jaffe DR, Garvin-Darby K, Morgan A, Manduchi E, Schug J, Kaestner KH. Advanced precision modeling reveals divergent responses of hepatocellular carcinoma to combinatorial immunotherapy. Cancer Commun (Lond). 2023 Jun;43(6):706-710.

Xiao Z, Todd L, Huang L, Noguera-Ortega E, Lu Z, Huang L, Kopp M, Li Y, Pattada N, Zhong W, Guo W, Scholler J, Liousia M, Assenmacher CA, June CH, Albelda SM, Puré E. Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors. Nat Commun. 2023 Aug 22;14(1):5110.

Robles-Matos N, Radaelli E, Simmons RA, Bartolomei MS. Preconception and developmental DEHP exposure alter liver metabolism in a sex-dependent manner in adult mouse offspring. Toxicology. 2023 Oct 6;499:153640.

Rotolo A, Whelan EC, Atherton MJ, Kulikovskaya I, Jarocha D, Fraietta JA, Kim MM, Diffenderfer ES, Cengel KA, Piviani M, Radaelli E, Duran-Struuck R, Mason NJ. Unedited allogeneic iNKT cells show extended persistence in MHC-mismatched canine recipients. Cell Rep Med. 2023 Oct 17;4(10):101241.

Bradbury AM, Bagel J, Swain G, Miyadera K, Pesayco JP, Assenmacher CA, Brisson B, Hendricks I, Wang XH, Herbst Z, Pyne N, Odonnell P, Shelton GD, Gelb M, Hackett N, Szabolcs P, Vite CH, Escolar M. Combination hematopoietic stem cell transplantation and intravenous AAVrh10-mediated gene therapy in a canine model proves pivotal for translation of Krabbe disease therapy. Mol Ther. 2023 Nov 10:S1525-0016(23)00615-9.

Klima ML, Kruger KA, Goldstein N, Pulido S, Low AYT, Assenmacher CA, Alhadeff AL, Betley JN. Anti-inflammatory effects of hunger are transmitted to the periphery via projection-specific AgRP circuits. Cell Rep. 2023 Oct 31;42(11):113338.

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.