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.

Publications:

  1. 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, 2016 May 16. doi: 10.1038/onc.2016.163. [Epub ahead of print], 2016
  2. Hein AL, Seshacharyulu P, Rachagani S, Sheinin YM, Ponnusamy MP, Mumby MC, Ouellette MM, Batra SK & Yan Y. PR55α subunit of protein phosphatase 2A supports the tumorigenic and metastatic potential of pancreatic cancer cells by sustaining hyperactive oncogenic signaling, Cancer Research, 76(8):2243-53. PMID: 26893480, 2016
  3. Yan Y & Ouellette MM. Rac1 GTPase in pancreatic cancer. Aging, 7(9): 609–610, 2015
  4. 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
  5. 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
  6. 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
  7. Yan Y, Hein A, Greer PM, Wang Z, Kolb RH, Batra SK & Cowan KH. A novel function of HER2/Neu in the activation of G2/M checkpoint in response to g-irradiation. Oncogene, 9 34(17):2215-26. PMC4362969, 2015
  8. Yan Y, Hein A, Etekpo A, Burchett KM, Lin C, Enke CA, Batra SK, Cowan KH & Ouellette MM. Inhibition of RAC1 GTPase sensitizes pancreatic cancer to γ-irradiation. Oncotarget, 5(21):10251-70, PMC4279370, 2014
  9. Hein LA, Ouellette MM & Yan Y. Radiation-induced signaling pathways that promote cancer cell survival. International Journal of Oncology, 45: 1813-1819, 2014
  10. Burchett KM, Yan Y & Ouellette MM. Telomerase inhibitor imetelstat (GRN163L) limits the lifespan of pancreatic cancer cells. PLoS One, 9(1): e85155, PMCID: PMC3883701, 2014
  11. 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
  12. 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
  13. Pandey P, Seshacharyulu P, Das S, Rachagani S, Ponnusamy MP, Yan Y, Johansson SL, Datta K, Lin MF & Batra SK. Impaired expression of protein phosphatase 2A subunits enhances metastatic potential of human prostate cancer cells through activation of AKT pathway. Br J Cancer, 1–11 | doi: 10.1038/bjc.2013.160. PMID: 23598299, 2013
  14. Kolb RH, Greer PM, Cao PT, Cowan KH & Yan Y. ERK1/2 signaling plays an important role in topoisomerase II poison-induced G2/M checkpoint activation. PLoS One, 7(11):1-16. PMID: 23166842, 2012
  15. Pessetto ZY, Yan Y, Bessho T & Natarajan A. Inhibition of BRCT(BRCA1)-phosphoprotein interaction enhances the cytotoxic effect of Olaparib in breast cancer cells: A proof of concept study for synthetic lethal therapeutic option. Breast Cancer Res Treat, 134(2):511-517. PMID: 22562176, 2012
  16. Yan Y, Greer PM, Cao PT, Kolb RH & Cowan KH. RAC1 GTPase plays an important role in g-irradiation induced G2/M checkpoint activation. Breast Cancer Research, 14(2):R60. PMID: 22494620, 2012
  17. Golla RM, Li M, Shen Y, Ji M, Yan Y, Fu K, Greiner TC, McKeithan TW & Chan WC. Inhibition of poly(ADP-ribose) polymerase (PARP) and ataxia telangiectasia mutated (ATM) on the chemosensitivity of mantle cell lymphoma to agents that induce DNA strand breaks. Hematol Oncol, 30(4):175-9. PMID: 22170260. No PMCID, 2011

Additional publications can be found through the link below:
https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/

Grants:

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

Pending

Title:  PR55alpha-associated PP2A in tumor progression and metastasis of pancreatic cancer NCI/ 1R01CA224767-A1 (MPI)
Funding Source:  NIH/NCI-R01
Principal Investigator:  Ying Yan & Surinder K. Batra (Multiple PI)
Role in Project:  Contacting Principal Investigator
Percent Effort:  25 %
Dates:  09/01/2018 - 08/31/2023
Total Direct Cost:  $2,633,750.00
Status:  Pending Scientific Review by TPM Study Section
Focus is on defining the mechanism by which PR55alpha-associated PP2A plays an essential role in pancreatic cancer progression and metastasis.

Title:  PR55alpha-associated PP2A in tumor progression and metastasis of pancreatic cancer NCI/ 1R01CA224767 (MPI)
Funding Source:  NIH/NCI-R01
Principal Investigator:  Ying Yan & Surinder K. Batra (Multiple PI)
Role in Project:  Principal Investigator
Percent Effort:  25%
Dates:  04/01/2018 - 03/31/2023
Total Direct Cost:  $2,633,750.00
Status:  25% (Impact score 33), TPM Study Section

Title:  Targeting Rac1 in triple negative breast cancer (NCI/ 1R01 CA227106-01A1)
Funding Source:  NIH/NCI-R01
Principal Investigator:  Ying Yan
Role in Project:  Principle Investigator
Percent Effort:  25%
Dates:  09/01/2018 – 08/31/2023
Total Direct Cost:  $1,881,250.00
Status:  Pending Scientific Review by BMCT Study Section
Focus is on defining the signaling mechanisms by which Rac1 promotes chemo/radio resistance of TNBC and test the Rac1’s potential as a therapeutic target for TNBC.

Title:  Targeting Rac1 in triple negative breast cancer (NCI/ 1R01 CA227106-01)
Funding Source:  NIH/NCI-R01
Principal Investigator:  Ying Yan
Role in Project:  Principle Investigator
Percent Effort:  25%
Dates:  04/01/2018 – 03/31/2023
Total Direct Cost:  $1,881,250.00
Status:  Percentile: 32, Impact Score: 43; BMCT study section

Title:  PP2A in Tumorigenesis of Pancreatic cancer NCI/ 1R01CA203485-01A1 (MPI)
Funding Source:  NIH/NCI-R01
Principal Investigator:  Ying Yan & Surinder K. Batra (Multiple PI)
Role in Project:  Principal Investigator
Percent Effort:  20%
Dates:  09/01/18 - 08/31/23
Total Direct Cost:  $2,633,750
Status:  16 % (Impact score of 27), MONC study section
Pending review for FY2018-IAeA-Co-funding Initiative

Title:  Structure Guided Design, Synthesis, and Evaluation of Rac1 Inhibitors for Pancreatic Cancer Therapy (1R01 CA228487-01)
Funding Source:  NIH/NCI-R01
Principal Investigator:  Ying Yan & Amar Nataranja
Role in Project:  Principle Investigator
Percent Effort:  20%
Dates:  04/01/2018 – 03/30/2023
Total Direct Cost:  $1,881,250.00
Status:  37%, Impact Score: 45, Study section: RG1 OTC-E (03), Center for Scientific Review Special Emphasis Panel
Action:  Plan to submit the revision by 07/05/2018

Title:  Nanoformulated doxorubicin combines with Rac1 inhibition for chemosensitization of triple negative breast cancer (1R01CA220051-01)
Funding Source:  NIH/NCI-R01
Principal Investigator:  Ying Yan
Role in Project:  Principle Investigator
Percent Effort:  25%
Dates:  07/01/2017 – 06/30/2022
Total Direct Cost:  $1,881,250.00
Status:  45%, DT study section