Ying Yan, Ph.D.

Ying Yan, Ph.D.Associate Professor

Education:
Postdoc - Biochemistry, Molecular Biology & Pharmacology, University of Texas Southwestern Medical Center, TX, 1999
Ph.D. - Cell Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, China, 1992

Professional Memberships:
American Association for Cancer Research
American Pancreatic Association
European Association for Cancer Research
European Academy of Tumor Immunology

Clinical & Research Interests:
Signal transduction pathways
Protein phosphatases and kinases
Cell cycle regulation and DNA damage checkpoint response
Molecular mechanisms of tumorigenesis and cancer metastasis
Molecular mechanisms of therapy resistance and cancer recurrence
Sensitization of cancer cells to chemo/radiation therapy

Research Projects:
Project 1: Rac1 as a therapeutic target in Triple Negative Breast cancer
Triple negative breast cancer (TNBC) has the poorest therapy outcome among breast cancer subtypes. Due to the lack of established therapeutic targets, the major treatment option for TNBC has been chemotherapy. However, a high rate of chemoresistance and recurrence have been the obstacles for improving overall survival of TNBC patients. Our published and preliminary data showed that Rac1 is overexpressed in human TNBC clinical samples and Rac1 level/activity is further enhanced in the TNBC cells resistant to the clinical protocol of chemo/radiation therapy. This project seeks to develop Rac1-based novel targeting therapeutics for TNBC, to increase therapy sensitivity and specificity, while simultaneously reduce systemic toxicity.

Project 2: Protein phosphatase 2A in pancreatic cancer
Pancreatic cancer remains the most lethal cancer mainly due to late diagnosis, aggressive nature, and therapeutic resistance. PP2A is a major serine/threonine protein phosphatase in human cells, which is composed of one catalytic subunit, one scaffolding subunit, and one regulatory subunit. While the scaffolding and catalytic subunits of PP2A are highly conserved, the different regulatory subunits of PP2A share no homology, which determines the substrate specificity and cellular localization of each PP2A holoenzyme complex. Our recent studies show that PP2A regulatory subunit PR55a is overexpressed in pancreatic cancer specimens and precursor lesions compared to normal pancreatic tissues. Furthermore, the overexpression of PR55a is correlated with poor patient survival. Consistently, knockdown of PR55α by shRNA in pancreatic cancer cells markedly diminishes the activities of several oncogenic signaling pathways, as well as transformed properties (proliferation, clonogenicity, anchorage-independent growth, and in vivo tumorigenicity). This research project is to investigate the critical role of PR55α-associated PP2A in the promotion of pancreatic tumorigenesis, aiming to discover new prognostic and therapeutic targets for pancreatic cancer.

Presentations:

  1. Hein AL, Schafer ND, Ouellette CY, Seshacharyulu P, Enke CA, Ouellette MM, Batra SK & Yan Y. PR55α regulatory subunit of PP2A inhibits the MOB1/LATS cascade and activates YAP in pancreatic cance AACR Symposia. San Diego, CA. May 2019
  2. Palanivel C, Gabler BM, Yan Y, Batra SK, and Ouellette MM. The small GTPase Rac1 controls the stability of Yes-Associated Protein (YAP) independently of the LATS1/2 kinases. AACR Symposia. San Diego, CA. May 2019
  3. Kelly G, Sonawane YA, Natarajan A, Ouellette M, and Yan Y Discovery of Rac1 Inhibitors for Breast and Pancreatic Cancer. UNMC Summer Undergraduate Research Program, UNMC. August 8, 2019

Publications:

  1. Hein AL, Brandquist ND, Ouellette CY, Seshacharyulu P, Enke CA, Ouellette MM, Batra SK, & Yan Y. PR55α regulatory subunit of PP2A inhibits the MOB1/LATS cascade and activates YAP in pancreatic cancer cells. Oncogenesis. 8(11):63, doi:10.1038/s41389-019-0172-9, 2019. PMC6817822
  2. Ouellette MM & Yan Y. Radiation-activated prosurvival signaling pathways in cancer cells. Precision Radiation Oncology. Epub Ahead of Print, DOI:10.1002/pro6.1076, 2019
  3. Tian T, Bi CF, Hein AL, Zhang X, Wang C, Shen SF, Enke C, Vose J, Yan Y & Fu K. Rac1 is a Novel Therapeutic Target in Mantle Cell Lymphoma. Blood Cancer Journal. 8:17, 2018.
  4. Burchett KM, Etekpo A, Batra SK, Yan Y & Ouellette MM. Inhibitors of telomerase and poly(ADP-ribose)polymerases synergize to limit the lifespan of pancreatic cancer cells. Oncotarget. 8(48):83754-83767, 2017
  5. Arnst JL, Hein AL, Taylor MA, Palermo NY, Contreras JI, Sonawane YA, Wahl AO, Ouellette MM, Natarajan A & Yan Y. Discovery and Characterization of Small Molecule Rac1 Inhibitors. Oncotarget, 8(21):34586-34600, 2017
  6. Seshacharyulua P, Baine MJ, Soucheka JJ, Menninga M, Kaura S, Yan Y, Ouellette MM, Jaina M, Lin C & Batra SK. Biological determinants of radioresistance and their remediation in pancreatic cancer. Biochimica et Biophysica Acta (BBA), 1868(1): 69–92, 2017
  7. Hein AL, Post CM, Sheinin YM, Lakshmanan I, Natarajan A, Enke CA, Batra SK, Ouellette MM & Yan Y. RAC1 GTPase promotes the survival of breast cancer cells in response to hyper-fractionated radiation treatment. Oncogene, 35(49):6319-6329, PMC5112160, 2016
  8. Yan Y & Ouellette MM. Rac1 GTPase in pancreatic cancer. Aging, 7(9): 609–610, 2015.
  9. Lakshmanan I., Seshacharyulu P., Haridas D., Rachagani S., Gupta S., Joshi S., Guda C., Yan Y, Jain M, Ganti AK, Ponnusamy MP & Batra SK. Novel HER3/MUC4 oncogenic signaling exacerbates the tumorigenic phenotypes of pancreatic cancer cells. Oncotarget 6(25):21085-99. PMID: 26035354, 2015
  10. Choi KH, Lakamp-Hawley AS, Kolar C, Yan Y, Borgstahl GEO & Ouellette MM. The Oligonucleotide/Oligosaccharide Binding fold 1 (OB1) of human POT1 recognizes both telomeric and nontelomeric DNA motifs. Biochimie, 115:17–27, PMC4500675, 2015
  11. Seshacharyulu P, Ponnusamy MP, Rachagani S, Lakshmanan I, Haridas D, Yan Y, Ganti AK & Batra SK. Targeting EGF-receptor(s) - STAT1 axis attenuates tumor growth and metastasis through downregulation of MUC4 mucin in human pancreatic cancer. Oncotarget, 6(7):5164-81, PMC4467140, 2015
  12. Hein LA, Ouellette MM & Yan Y. Radiation-induced signaling pathways that promote cancer cell survival. International Journal of Oncology, 45: 1813-1819, 2014
  13. Burchett KM, Yan Y & Ouellette MM. Telomerase inhibitor imetelstat (GRN163L) limits the lifespan of pancreatic cancer cells. PLoS One, 9(1): e85155, PMC3883701, 2014
  14. Peters HL, Yan Y & Solheim JC. APLP2 regulation of the expression of MHC class I molecules on irradiated Ewing’s sarcoma cells. OncoImmunology, 2(10): e26293. PMC3862638, 2013
  15. Peters HL, Yan Y, Nordgren TM, Cutucache CE, Joshi SS & Solheim JC. Amyloid precursor-like protein 2 reduces Ewing sarcoma cell radiosensitivity and is elevated in immune-evasive Ewing sarcoma cells. Cancer Biology & Therapy, 14:8, 752–760. PMID: 23792571, 2013

Additional publications can be found through the link below:

https://www.ncbi.nlm.nih.gov/myncbi/ying.yan.2/bibliography/public/

Grants:

Grants activity (FY2019)

PI – Pilot project, Role of Rho GTPases in the radioresponse of pancreatic cancer - Yan, DHHS/NIH/NIGMS, Federal. 08/01/2018 - 07/31/2019

PI - Pilot project, Determination of the interactions between PR55α and the Hippo pathway components. - Yan, DHHS/NIH/NIGMS, Federal. 04/01/2019 - 07/31/2019

Trainee - Proteomics Workshop Award- Yan, DHHS/ NIH / INBRE, Federal. 04/03/2019 - 04/05/2019

Funded

Title:  Rac1 GTPase in tumorigenesis and progression of pancreatic cancer (NCI / R01 CA206444-01)
Funding Source:  NIH-R01  
Principal Investigators:  Michel M. Ouellette and Surinder Batra (Multiple PI)
Role in Project:  Co-Investigator
Percent Effort:  5%
Dates:  05/01/2016 to 04/31/2021
Total Direct Cost:  $2,257,500

Title:  SPORE in Pancreatic Cancer (2 P50 CA127297-06A1)
Funding Source:  NIH/NCI
Contact PI / Project Leader:  Michael A. Hollingsworth, Ph.D.
Role in Project:  Co-Investigator of Project 4 (PI: Surinder K. Batra) "Radiosensitization of Pancreatic Cancer"
Percent Effort:  5%
Dates:  9/23/2014 – 8/31/2019
Total Direct Cost:  $3,852,432
Focus is on translational studies that address basic and clinical issues of importance to improving outcome of patients with pancreatic cancer.

Title:  Nebraska Center for Cellular Signaling
Funding Source:  NIH / NIGMS / 5P30GM106397
Contact PI / Project Leader:  Keith R Johnson, Ph.D.
Role in Project:  Principle Investigator of a Collaborative Pilot Project "Role of Rho GTPases in the radioresponse of pancreatic cancer"
Percent Effort:  5%
Dates:  11/01/2017 – 07/31/2019
Total Direct Cost:  $100,000

Title:  Nebraska Center for Cellular Signaling
Funding Source:  NIH / NIGMS, 5P30GM106397
Contact PI / Project Leader:  Keith R Johnson, Ph.D.
Role in Project:  Institutional Development Award (IDeA) "Determination of the interactions between PR55a and the Hippo pathway components"
Percent Effort:  N/A
Dates:  06/01/2017 – 05/30/2018
Total Direct Cost:  $2,500

Lectures

Title: “The Two Faces of PP2A in Cancer”, Fred & Pamela Buffett Cancer Center MEBP Seminar Series, UNMC, 01/25/2019

Title: “PP2A in Cancer: Tumor Promoter or Tumor Suppressor”, Department of Biochemistry and Molecular Biology Seminar Series, UNMC, 02/12/2019