LATEST NEWS

2022

Dr. Paust’s application  R21 AI170555 is awarded by the National Institute of Health (NIH/NIAID), titled: “Control of HIV-induced MDSC expansion and immunosuppression by cytotoxic lymphocytes.”

Post-doctoral positions are available in the Paust lab as of January 2023:

https://recruiting2.ultipro.com/SCR1003TSRI/JobBoard/98759e7d-7ede-4c0b-ac7b-2c6293c7b522/OpportunityDetail?opportunityId=dcea6353-1bf9-414f-9c8e-894ef8b9f1d7

 

2021

Dr. Paust’s application R01 AI-161014 is awarded by the National Institute of Health (NIH/NIAID), titled: “How antigen exposure shapes the subsequent NK cell response to HIV.”

RESEARCH

Members of the Paust laboratory are interested in the development and testing of novel immunotherapies that elicit clinically relevant Natural Killer cell-mediated anti-pathogen or anti-tumor immunity. Our research program is centered on the discovery that subsets of NK cells are long-lived and capable of antigen-specific immunological memory to viruses and altered self, giving precedence to investigations that seek to exploit NK cell activity to prevent or cure disease. Currently, we are pursuing three specific scientific goals: 1) Identification of the mechanisms by which subsets of murine and human NK cells mediate antigen-specific immunological memory responses; 2) Identification of NK cell-specific immune correlates of protection from infection or malignancy; 3) Development of effective, host-protective vaccine or therapeutic approaches that elicit potent NK cell-mediated recall responses in vivo. To enable our studies, we routinely utilize mouse models, xenograft models, and clinical samples for the immunological analyses of innate and adaptive NK cell-mediated immune responses.

SILKE PAUST, PHD

Associate Professor
Department of Immunology and Microbiology

Scripps Research Joint Appointments
Associate Professor, Department of Immunology and Microbiology
Faculty, Graduate Program

Other Joint Appointments
2018 –
Member, The San Diego Center for Precision Immunotherapy in the Moores Cancer Center, UC San Diego, San Diego, CA
2018 –
Member, Center for Aids Research, San Diego, CA

Education
Ph.D., Immunology, Harvard University, 2005

BIOSKETCH

ACTIVE FUNDING

R01 AI-130065
Role: PI
Sponsor: National Institute of Health (NIH/NIAID)
Mechanisms of Protection of Universal Therapeutic Antibodies to Influenza A
The goal of this project is to develop a universal prophylactic or therapeutic agent to prevent or treat influenza A infection and associated pathologies.

1R01CA254268 (WHITE)

Role: Co-I
Sponsor: National Institute of Health (NIH/NCI)
Combining Irreversible Electroporation with Immunotherapy for the Systemic Treatment of Pancreatic Cancer.
The goal of this project is to evaluate Irreversible Electroporation with Immunotherapy for the Systemic Treatment of Pancreatic Cancer, using mouse and humanized mouse models of pancreatic cancer.

R01 AI-161014
Role: PI
Sponsor: National Institute of Health (NIH/NIAID)
How antigen exposure shapes the subsequent NK cell response to HIV
This study will identify the NK functional subsets that are most responsive to HIV, and their mechanisms of host protection from HIV disease, providing the rationale to develop novel vaccines that exploit the antiviral effector functions of NK cells to protect humans from HIV infection while avoiding harmful activity.

R01AI154138 (WU)
Role: Co-I
Sponsor: National Institute of Health (NIH/NIAID)
Exploring Siglec-glycan ligand interactions using chemoenzymatic approaches
This project is to use a combination of chemoenzymatic, biochemical and genetic tools to study Siglec biology and their therapeutic implication.

PERSONNEL

 

 

 

ALUMNI

Lynn H. Bimler, Ph.D. Postdoctoral associate, Baylor College of Medicine
Rana Nikzad, Ph.D. Principal Scientist, Kiadis, a Sanofi Company
Kevin Aviles-Padilla, Ph.D. Associate Scientist, Immatics
Laura S. Angelo, Ph.D. Assistant Professor, Baylor College of Medicine
Vipul Singh, Ph.D. Research Associate, UT-Texas, Houston Methodist
Ashleigh R. Murphy Schafer, Ph.D. Epidemiologist (Molecular Specialist), San Diego County Public Health Services Laboratory
Blake Heath, Ph.D. Scientist I, GentiBio
Duy Tri Le, B.S. Graduate Student, Baylor College of Medicine
Emily Haines, M.S., MPH Medical student, Washington University, St. Louis, MO
Grahame Hogg, B.S. Medical Student, Washington University School of Biology Instructor at El Paso Community College
Dwight Fan, B.S. Medical Student, Baylor College of Medicine
Amber Song, B.S. Medical Student, Baylor College of Medicine

LABORATORY ACTIVITIES

PUBLICATIONS

2022

CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation. Aviles-Padilla K, Angelo LS, Fan D, Paust S. Front Immunol. 2022 Jun 29;13:886835. doi: 10.3389/fimmu.2022.886835. PMID: 35844621; PMCID: PMC9277058.

M2e-specific monoclonal antibody cocktails against inflenza A virus are superior to individual monoclonal antibody treatments, universally effective, and viral escape mutant…  LH Bimler, T Kim, SL Ronzulli, AY Song, SK Johnson, CA Jones, … bioRXiv April 3, 2022

Hematopoietic stem and progenitor cells improve survival from sepsis by boosting immunomodulatory cells. DE Morales-Mantilla, B Kain, D Le, AR Flores, S Paust, KY King. Elife 11, e74561, 2022

Phenotypic and Functional Plasticity of CXCR6+ Peripheral Blood NK Cells. Laura S. Angelo Graham D. Hogg Shawn Abeynaike Lynn Bimler Alexander Vargas-Hernandez Silke Paust Silke Paust and Paust S, Angelo L. Frontiers in immunology, vol. 12, Jan 1, 2022.

 

2021

Divergent Mast Cell Responses Modulate Antiviral Immunity During Influenza Virus Infection. Murphy-Schafer, Ashleigh R and Paust, Silke. Frontiers in cellular and infection microbiology, vol. 11, pp. 580679, 2021.

Humanized Mice for the Evaluation of Novel HIV-1 Therapies. Abeynaike, Shawn and Paust, Silke. Frontiers in immunology, vol. 12, pp. 636775, 2021.

IL-10 normalizes aberrant amygdala GABA transmission and reverses anxiety-like behavior and dependence-induced escalation of alcohol intake. Patel, Reesha R Wolfe, Sarah A Bajo, Michal Abeynaike, Shawn Pahng, Amanda Borgonetti, Vittoria D’Ambrosio, Shannon Nikzad, Rana Edwards, Scott Paust, Silke Roberts, Amanda J and Roberto, Marisa. Progress in neurobiology, vol. 199, pp. 101952, Apr 2021.

Matrix Protein 2 Extracellular Domain-Specific Monoclonal Antibodies Are an Effective and Potentially Universal Treatment for Influenza A. Bimler, Lynn Ronzulli, Sydney L. Song, Amber Y. Johnson, Scott K. Jones, Cheryl A. Kim, Teha Le, Duy T. Tompkins, S. Mark and Paust, Silke. Journal of Virology, vol. 95.

Natural Killer Cell Interactions With Myeloid Derived Suppressor Cells in the Tumor Microenvironment and Implications for Cancer Immunotherapy. Zalfa, Cristina and Paust, Silke. Frontiers in immunology, vol. 12, pp. 633205, May 5, 2021.

Natural killer cells and cytotoxic T-lymphocytes are required to clear solid tumor in a patient-derived-xenograft. Le, Duy T. Huynh, Tridu R. Burt, Bryan M. Buren, George Van Abeynaike, Shawn A. Zalfa, Cristina Nikzad, Rana Kheradmand, Farrah Tyner, John J. and Paust, Silke. JCI Insight.

 

2020

Resistance to natural killer cell immunosurveillance confers a selective advantage to polyclonal metastasis. Hin Ching Lo, Zhan Xu, Ik Sun Kim, Bradley Pingel, Sergio Aguirre, Srikanth Kodali, Jun Liu, Weijie Zhang, Aaron M Muscarella, Sarah M Hein, Alexander S Krupnick, Joel R Neilson, Silke Paust, Jeffrey M Rosen, Hai Wang, Xiang H-F Zhang. Nature Cancer 1 (7), 709-722

Alcohol dependence promotes systemic IFN-y and IL-17 responses in mice.  K Frank, S Abeynaike, R Nikzad, RR Patel, AJ Robert, M Roberto,… Plos One 15 (12), e0239246

Dynamic Natural Killer Cell and T Cell Responses to Influenza Infection. Frank, Kayla and Paust, Silke. Frontiers in cellular and infection microbiology, vol. 10, pp. 425, 2020.

Human NK cell deficiency as a result of biallelic mutations in MCM10. Mace, Emily M. Paust, Silke Conte, Matilde I. Baxley, Ryan M. Schmit, Megan M. Patil, Sagar L. Guilz, Nicole C. Mukherjee, Malini Pezzi, Ashley E. Chmielowiec, Jolanta Tatineni, Swetha, et al. Journal of Clinical Investigation.

NK cells and CTLs are required to clear solid tumor in a novel model of patient-derived-xenograft. Le, Duy Tri Burt, Bryan Buren, George Van Abeynaike, Shawn A Zalfa, Cristina Nikzad, Rana Kheradmand, Farrah and Paust, Silke. Cold Spring Harbor Laboratory

 

2019

AuNP-M2e+sCpG vaccination of juvenile mice generates lifelong protective immunity to influenza A virus infection. Bimler, Lynn Song, Amber Y. Le, Duy T. Schafer, Ashleigh Murphy and Paust, Silke. Immunity & Ageing, vol. 16.

CXCR6 + NK Cells in Human Fetal Liver and Spleen Possess Unique Phenotypic and Functional Capabilities. Angelo, Laura S Bimler, Lynn H Nikzad, Rana Aviles-Padilla, Kevin and Paust, Silke. Frontiers in immunology, vol. 10, pp. 469, 2019.

Effect of recent seasonal influenza vaccination on serum antibody responses to candidate pandemic influenza A/H5N1 vaccines: A meta-analysis. Keitel, W.A Voronca, D.C Atmar, R.L Paust, S Hill, H Wolff, M.C and Bellamy, A.R. Vaccine, vol. 37, (no. 37), pp. 5535-5543, 2019.

Human natural killer cells mediate adaptive immunity to viral antigens. Nikzad, Rana Angelo, Laura S Aviles-Padilla, Kevin Le, Duy T Singh, Vipul K Bimler, Lynn Vukmanovic-Stejic, Milica Vendrame, Elena Ranganath, Thanmayi Simpson, Laura Haigwood, Nancy L Blish, Catherine A Akbar, Arne N and Paust, Silke. Science immunology, vol. 4, (no. 35), May 10, 2019.

 

2018

IL17A Regulates Tumor Latency and Metastasis in Lung Adeno and Squamous SQ.2b and AD.1 Cancer. You, Ran R, You DeMayo, Francesco J FJ, DeMayo Liu, Jian J, Liu SN, Cho Cho, Sung-Nam Burt, Bryan M BM, Burt CJ, Creighton, et al. Cancer immunology research.

Mosquito saliva alone has profound effects on the human immune system. MB, Vogt A, Lahon RP, Arya AR, Kneubehl JL, Spencer Clinton S, Paust and R, Rico-Hesse. PLoS neglected tropical diseases.

 

2017

AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity. D, Liang L, Tian R, You MM, Halpert V, Konduri YC, Baig S, Paust D, Kim S, Kim F, Jia S, Huang, et al. Frontiers in immunology.

Cancer Immunotherapy: Historical Perspective of a Clinical Revolution and Emerging Preclinical Animal Models. WK, Decker Silva RF MH, Sanabria LS, Angelo F, Guimarães BM, Burt F, Kheradmand and S, Paust. Frontiers in immunology.

Consensus M2e peptide conjugated to gold nanoparticles confers protection against H1N1, H3N2 and H5N1 influenza A viruses. W, Tao BL, Hurst AK, Shakya MJ, Uddin RS, Ingrole M, Hernandez-Sanabria RP, Arya L, Bimler S, Paust EB, Tarbet EB, Tarbet and HS, Gill

Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients. Silva RF A, Yoshida DM, Cardozo RM, Jales S, Paust S, Derchain and F, Guimarães. International journal of molecular sciences.

p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy. M, Moreno-Smith A, Lakoma Z, Chen L, Tao KA, Scorsone L, Schild K, Aviles-Padilla R, Nikzad Y, Zhang R, Chakraborty JJ, Molenaar SA, Vasudevan and E, Barbieri. Clinical cancer research : an official journal of the American Association for Cancer Research.

Redefining Memory: Building the Case for Adaptive NK Cells. S, Paust CA, Blish and RK, Reeves. Journal of virology.

 

2016

Biallelic mutations in IRF8 impair human NK cell maturation and function. Mace, Emily M EM, Mace V, Bigley Bigley, Venetia JT, Gunesch Gunesch, Justin T Chinn, Ivan K IK, Chinn Angelo, Laura S LS, Angelo MA, Care, et al. The Journal of clinical investigation.

Chemo-immunotherapy mediates durable cure of orthotopic KrasG12D/p53-/- pancreatic ductal adenocarcinoma. V, Konduri D, Li MM, Halpert D, Liang Z, Liang Y, Chen WE, Fisher S, Paust JM, Levitt QC, Yao and WK, Decker. Oncoimmunology.

Dendritic Cell-Secreted Cytotoxic T-Lymphocyte-Associated Protein-4 Regulates the T-cell Response by Downmodulating Bystander Surface B7. MM, Halpert V, Konduri D, Liang Y, Chen JB, Wing S, Paust JM, Levitt and WK, Decker. Stem cells and development.

Liver is liver and blood is blood, and finally the twain have met. KD, Bissig S, Paust and M, Barzi. Journal of hepatology.

Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation. T, Sekine Sekine, Takuya Sekine, Takuya Sekine, Takuya Sekine, Takuya Sekine, Takuya Sekine, Takuya Sekine, Takuya Sekine, Takuya Sekine, Takuya Sekine, Takuya, et al. Blood.

 

2015

Daring to learn from humanized mice. S, Paust and M, Bettini. Blood.

 

2014

Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation. L, Riol-Blanco Riol-Blanco, Lorena J, Ordovas-Montanes Ordovas-Montanes, Jose M, Perro Perro, Mario Naval, Elena E, Naval Thiriot, Aude A, Thiriot D, Alvarez, et al. Nature.

 

2013

Natural killer cell-mediated contact sensitivity develops rapidly and depends on interferon-α, interferon-γ and interleukin-12. Majewska-Szczepanik, Monika M, Majewska-Szczepanik Paust, Silke S, Paust Von Andrian, Ulrich Andrian UH PW, Askenase Askenase, Philip W Szczepanik, Marian and M, Szczepanik. Immunology.

 

2011

Natural killer cell memory. Paust, Silke Paust, S. Von Andrian, Ulrich and Von Andrian, U.H. Nature Immunology, vol. 12, pp. 500-508.

 

2012

Adaptive immunity mediated by Natural Killer cells. (45.20) S Paust, M Flynn, B Wang, S Dougan, H Ploegh, A Telenti, R Compans, … The Journal of Immunology 188 (1 Supplement), 45.20-45.20

 

2010

Adaptive immune responses mediated by natural killer cells. Paust, Silke Paust, S. Senman, Balimkiz Senman, B. Von Andrian, Ulrich and Von Andrian, U.H. Immunological Reviews, vol. 235, pp. 286-296.

Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses. Paust, Silke S, Paust Gill, Harvinder S HS, Gill Wang, Bao-Zhong BZ, Wang Flynn, Michael P MP, Flynn Moseman, E. A EA, Moseman B, Senman, et al. Nature immunology.

 

2005

Regulatory T cells and autoimmune disease. Paust, Silke S, Paust Cantor, Harvey I and H, Cantor. Immunological reviews.

 

2004

Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Paust, Silke S, Paust L, Lu Lu, Linrong Mc Carty, Nami N, McCarty Cantor, Harvey I and H, Cantor. Proceedings of the National Academy of Sciences of the United States of America.

Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes. Mc Carty, Nami N, McCarty Paust, Silke S, Paust Ikizawa, Koichi K, Ikizawa Dan, Ippeita I, Dan Li, Xiaoyan X, Li Cantor, Harvey I and H, Cantor. Nature immunology.

 

1999

Cutting edge: the tyrosine phosphatase SHP-1 regulates thymocyte positive selection. Plas, D R DR, Plas Williams, Calvin B CB, Williams Kersh, G J GJ, Kersh White, L S LS, White White, J M JM, White S, Paust. Journal of immunology (Baltimore, Md. : 1950).

Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22. J, Blasioli S, Paust and ML, Thomas. The Journal of biological chemistry.