Pathology News 2021

October 2021

PUBLICATIONS

Harrell Lab: Identification of nuclear export inhibitor-based combination therapies in preclinical models of triple-negative breast cancer. Narmeen S.Rashid, Nicole S. Hairr, Graeme Murray, Amy L. Olex, Tess J. Leftwich, Jacqueline M. Grible, Jason Reed, Mikhail G. Dozmorovaf, J. Chuck Harrell. https://www.sciencedirect.com/science/article/pii/S1936523321002278?via%3Dihub

June 2021

PUBLICATIONS

Unmasking BCL-2 Addiction in Synovial Sarcoma by Overcoming Low NOXA.  Fairchild CK Jr, Floros KV, Jacob S, Coon CM, Puchalapalli M, Hu B, Harada H, Dozmorov MG, Koblinski JE, Smith SC, Domson G, Leverson JD, Souers AJ, Takebe N, Ebi H, Faber AC, Boikos SA. Cancers (Basel). 2021 May 12;13(10):2310. doi: 10.3390/cancers13102310. https://pubmed.ncbi.nlm.nih.gov/34065859/

Serine residues 726 and 780 have nonredundant roles regulating STAT5a activity in luminal breast cancer.  Woock AE, Grible JM, Olex AL, Harrell JC, Zot P, Idowu M, Clevenger CV. Sci Rep. 2021 Jun 29;11(1):13506. doi: 10.1038/s41598-021-92830-8. https://pubmed.ncbi.nlm.nih.gov/34188118/

OTHER

Bos Lab press:  The V Foundation for Cancer Research hosted its annual Virginia Vine on April 24, 2021 and raised a record $1 million. One of the VCU Massey Cancer Center researchers highlighted at the event was Paula Bos, member of the Cancer Biology research program at Massey and assistant professor in the Department of Pathology at the VCU School of Medicine. During this virtual tour of her laboratory, Bos explains the research funded by V Scholar Grants. https://www.youtube.com/watch?v=BXdT358h910


Harrell Lab press:  https://blog.komen.org/blog/is-it-possible-to-stop-drug-resistance-and-breast-cancer-metastasis-dr-chuck-harrell-is-working-to-find-out/

Chuck Harrell was promoted to Associate Professor with tenure.

Senthil Radhakrishnan was promoted to Associate Professor with tenure.

April 2021

Jackie Grible, Postdoctoral Fellow

PUBLICATIONS

The human intermediate prolactin receptor is a mammary proto-oncogene. Jacqueline M Grible, Patricija Zot, Amy L Olex, Shannon E Hedrick, J Chuck Harrell, Alicia E Woock, Michael O Idowu, Charles V Clevenger
NPJ Breast Cancer. 2021 Mar 26;7(1):37. doi: 10.1038/s41523-021-00243-7.PMID: 33772010
https://pubmed.ncbi.nlm.nih.gov/33772010/

GRANTS

Dr. Senthil Radhakrishnan

Senthil Radhakrishnan was awarded a grant from the American Cancer Society. "Understanding and Targeting Nrf1 Pathway in Triple-negative Breast Cancer"
$165,000 direct/year for 4 years Co-I: Harrell, Koblinski, Gewirtz, McClay

OTHER

Justin Craig completed the requirements for a Degree of Doctor of Philosophy in the Clinical and Translational Science Program
 
Alicia Woock completed the requirements for a Degree of Doctor of Philosophy in the Clinical and Translational Science Program

A publication from Justin Craig, Tia Turner, Chuck Harrell, and Charles Clevenger is the current featured article by the Endocrine Society.  https://academic.oup.com/endo

A publication from Tia Turner, Mohammad Alzubi, and Chuck Harrell is included in Scientific Reports Top 100 downloaded cancer papers for 2020, at 25th. https://www.nature.com/collections/aijhgffdjh

March 2021

Bos Lab
Regulatory T Cells Support Breast Cancer Progression by Opposing IFN-γ-Dependent Functional Reprogramming of Myeloid Cells.
Clark NM, Martinez LM, Murdock S, deLigio JT, Olex AL, Effi C, Dozmorov MG, Bos PD.
Cell Rep. 2020 Dec 8;33(10):108482. doi: 10.1016/j.celrep.2020.108482.
https://pubmed.ncbi.nlm.nih.gov/33296659/

Local Targeting of Lung-Tumor-Associated Macrophages with Pulmonary Delivery of a CSF-1R Inhibitor for the Treatment of Breast Cancer Lung Metastases.
Alhudaithi SS, Almuqbil RM, Zhang H, Bielski ER, Du W, Sunbul FS, Bos PD, da Rocha SRP.
Mol Pharm. 2020 Dec 7;17(12):4691-4703. doi: 10.1021/acs.molpharmaceut.0c00983. Epub 2020 Nov 10.
PMID: 33170724
https://pubmed.ncbi.nlm.nih.gov/33170724/

Harrell and Clevenger Labs
Breast cancer liver metastasis: current and future treatment approaches.
Rashid NS, Grible JM, Clevenger CV, Harrell JC.
Clin Exp Metastasis. 2021 Mar 6. doi: 10.1007/s10585-021-10080-4. Online ahead of print.
https://pubmed.ncbi.nlm.nih.gov/33675501/

Prolactin Drives a Dynamic STAT5A/HDAC6/HMGN2 Cis-Regulatory Landscape Exploitable in ER+ Breast Cancer.
Craig JM, Turner TH, Harrell JC, Clevenger CV.
Endocrinology. 2021 Feb 16:bqab036. doi: 10.1210/endocr/bqab036. Online ahead of print.
https://pubmed.ncbi.nlm.nih.gov/33589921/

Harrell and Bos Labs
Unexpected PD-L1 immune evasion mechanism in TNBC, ovarian, and other solid tumors by DR5 agonist antibodies.
Mondal T, Shivange GN, Tihagam RG, Lyerly E, Battista M, Talwar D, Mosavian R, Urbanek K, Rashid NS, Harrell JC, Bos PD, Stelow EB, Stack MS, Bhatnagar S, Tushir-Singh J.
EMBO Mol Med. 2021 Mar 5;13(3):e12716. doi: 10.15252/emmm.202012716. Epub 2021 Feb 15.
https://pubmed.ncbi.nlm.nih.gov/33587338/

Koblinski Lab
MYCN-amplified neuroblastoma is addicted to iron and vulnerable to inhibition of the system Xc-/glutathione axis.
Floros KV, Cai J, Jacob S, Kurupi R, Fairchild CK, Shende M, Coon CM, Powell KM, Belvin BR, Hu B, Puchalapalli M, Ramamoorthy S, Swift K, Lewis JP, Dozmorov MG, Glod J, Koblinski JE, Boikos SA, Faber AC.
Cancer Res. 2021 Jan 22:canres.1641.2020. doi: 10.1158/0008-5472.CAN-20-1641. Online ahead of print.
https://pubmed.ncbi.nlm.nih.gov/33483374/

Conformational Modulation of Iduronic Acid-Containing Sulfated Glycosaminoglycans by a Polynuclear Platinum Compound and Implications for Development of Antimetastatic Platinum Drugs.
Gorle AK, Haselhorst T, Katner SJ, Everest-Dass AV, Hampton JD, Peterson EJ, Koblinski JE, Katsuta E, Takabe K, von Itzstein M, Berners-Price SJ, Farrell NP.
Angew Chem Int Ed Engl. 2021 Feb 8;60(6):3283-3289. doi: 10.1002/anie.202013749. Epub 2020 Dec 23.
https://pubmed.ncbi.nlm.nih.gov/33174390/ 

Atfi Lab
Hsp70 acts as a fine-switch that controls E3 ligase CHIP-mediated TAp63 and ΔNp63 ubiquitination and degradation.
Wu HH, Wang B, Armstrong SR, Abuetabh Y, Leng S, Roa WHY, Atfi A, Marchese A, Wilson B, Sergi C, Flores ER, Eisenstat DD, Leng RP.
Nucleic Acids Res. 2021 Feb 22:gkab081. doi: 10.1093/nar/gkab081. Online ahead of print.
https://pubmed.ncbi.nlm.nih.gov/33619536/

Human Papillomavirus 16 (HPV16) E2 Repression of TWIST1 Transcription Is a Potential Mediator of HPV16 Cancer Outcomes.
Fontan CT, Das D, Bristol ML, James CD, Wang X, Lohner H, Atfi A, Morgan IM.
https://pubmed.ncbi.nlm.nih.gov/33298572/

Loss of Jag1 cooperates with oncogenic Kras to induce pancreatic cystic neoplasms.
Chung WC, Challagundla L, Zhou Y, Li M, Atfi A, Xu K.
Life Sci Alliance. 2020 Dec 2;4(2):e201900503. doi: 10.26508/lsa.201900503. Print 2021 Feb.
https://pubmed.ncbi.nlm.nih.gov/33268505/  

GRANTS:

Youngman Oh, (pictured) School of Medicine VETAR grant.  “Development of a novel targeted therapy for age-related macular degeneration”. A MultiPI application with Dr. Qinggu Xu in Pharmaceutics to investigate therapeutic potential of IGFBP-3R mAb for dry AMD using a sodium iodate AMD mouse model.

Michael Idowu and Chuck Harrell are Co-Investigators on a R01 from the NCI, with PI David Gewirtz (Pharmacology): A sequential therapeutic strategy of senescence induction and senolytics for elimination of surviving residual breast tumor cells. $3.3M

OTHER:
Chuck Harrell served on the NIH MCT2 study section March 3-5.

May 2021

PUBLICATIONS

Autophagy-Dependent Sensitization of Triple-Negative Breast Cancer Models to Topoisomerase II Poisons by Inhibition of The Nucleosome Remodeling Factor. Tyutyunyk-Massey L, Sun Y, Dao N, Ngo H, Dammalapati M, Vaidyanathan A, Singh M, Haqqani S, Haueis J, Finnegan R, Deng X, Kirberger SE, Bos PD, Bandyopadhyay D, Pomerantz WCK, Pommier Y, Gewirtz DA, Landry JW. Mol Cancer Res. 2021 Apr 2. doi: 10.1158/1541-7786.MCR-20-0743. Online ahead of print. PMID: 33811160
https://pubmed.ncbi.nlm.nih.gov/33811160/

Cancer-Mediated Muscle Cachexia: Etiology and Clinical Management. Siff T, Parajuli P, Razzaque MS, Atfi A. Trends Endocrinol Metab. 2021 Apr 19:S1043-2760(21)00068-0. doi: 0.1016/j.tem.2021.03.007. Online ahead of print. PMID: 33888422
https://pubmed.ncbi.nlm.nih.gov/33888422/

Chromatin conformation capture (Hi-C) sequencing of patient-derived xenografts: analysis guidelines.
Dozmorov MG, Tyc KM, Sheffield NC, Boyd DC, Olex AL, Reed J, Harrell JC.
Gigascience. 2021 Apr 21;10(4):giab022. doi: 10.1093/gigascience/giab022.
PMID: 33880552
https://pubmed.ncbi.nlm.nih.gov/33880552/