The overall research goal in our lab is to identify molecular mechanisms of immunosuppression and evasion in brain cancer or metastasis and develop novel immunotherapeutic for these diseases.  Glioblastoma is one of the most aggressive cancer with dismal 5-year survival rate less than 5% and remains incurable. The unique tumor microenvironment in the brain is extremely challenging for effective therapies. The current standard of care for GBM is a combination of surgery, chemotherapy and radiation, which are of limited efficacy and often cause devastating neurological side effects. Therefore, safer and more effective therapeutic modalities are needed for GBM. In addition, an estimated 24-45% of all cancer patients in the U.S. have brain metastases. Development of brain metastasis remains a substantial contributor to overall cancer mortality.

Immunotherapies including immune checkpoint blockade or CAR-T therapy have transformed cancer treatment in multiple cancers but have not demonstrated clinical benefits in large scale clinical trial for brain cancer or CNS metastasis. Previously, we showed that the pharmacological inhibition of Protein Phosphatase 2A (PP2A) enhances the antitumor efficacy of anti-PD-1 antibodies in PD-1 blockade-resistant melanoma and colon cancer models. Building on this work, we found that PP2A inhibition sensitizes a mouse model of glioblastoma (GBM) to immune checkpoint therapy (ICT), and these findings have led to a phase II clinical trial testing PP2A inhibition as a single agent for recurrent GBM to assess the degree of drug penetration into brain tumor (NCT03027388).

In our lab, currently we focus on the following areas:

1. Cross-talk between immune cells and cancer cells in the brain.
2. Relationship between cancer metabolism and immune suppression.

Maggio D, Ho WS, Breese R, Walbridge S, Wang H, Heiss JD, Gilbert MR,Kovach JS, Lu R*, Zhuang Z. Inhibition of protein phosphatase-2A with PD-1 blockade enhances antitumor immunity and survival in glioblastoma. Under Revision, OncoImmunology 2019. *Co-corresponding author.

Bedognetti D, Ceccarelli M, Lu R*, …, the Society for Immunotherapy of Cancer (SITC) Cancer Immune Responsiveness Task Force and Working Groups. A comprehensive view on cancer immune responsiveness: A synopsis from the SITC workshop. J Immunother Cancer. 2019 *Co-first author.

Ho W, Wang H, Heiss J, Gilbert MR, Lu R*, Zhuang Z. Pharmacological inhibition of protein phosphatase-2A, with novel inhibitor LB-100, achieves durable immune-mediated antitumor activity when combined with PD-1 blockade. Nat Commun. 2018 May 29;9(1):2126. * Corresponding author.

Danaher P, Warren S, Lu R, Sullivan A, Samayoa J, Marincola F, Pekker I, Wallden B, Cesano A. Pan-cancer Adaptive Immune Resistance as Defined by The Tumor Inflammation (TIS): Results from The Cancer Genome Atlas (TCGA). J Immunother Cancer. 2018 Jun 22;6(1):63.

Turan T, Kannan D, Patel M, Barnes JM, Tanlimco S, Lu R, Halliwill K, Kongpachith S, Kline D, Hendrickx W, Cesano A, Butterfield LH, Kauffman H, Hudson T, Bedognetti D, Marincola F, Samayoa J. Immune Oncology, Immune Responsiveness and the Theory of Everything. J Immunother Cancer. 2018 Jun 5;6(1):50.

Ho W, Sizdahkhani S, Hao S, Song H , Seldomridge A, Tandle A, Maric D, Kramp T, Lu R , Heiss J, Camphausen K , Gilbert MR , Zhuang Z , Deric M. Park . LB-100, a novel Protein Phosphatase 2A Inhibitor (PP2A), Sensitizes Malignant Meningioma Cells to the Therapeutic Effects of Radiation. Cancer Lett. 2018 Feb 28;415:217-226.

Lu R*, Turan T, Samayoa J, Marincola FM. Cancer Immune Resistance: Can Theories Converge? Emerging Topics in Life Sciences. 2017 Dec 1(5):411. *Corresponding author.

Rutz S, Kayagaki N, Phung QT, Eidenschenk C, Noubade R, Lesch J, Lu R, Newton K, Huang OW,Cochran AG, DeVoss J, Webster J, Diehl L, Kirkpatrick DS, Lill JR, Ouyang W, Dixit VM. Deubiquitinase DUBA is a post-translational brake on interleukin-17 production in T cells. Nature. 2015 Feb 19;518(7539):417-21.

Noubade R, Wong K, Ota N, Rutz S, Eidenschenk C, Valdez PA, Ding J, Peng I, Sebrell A, Caplazi P, DeVoss J, Soriano RH, Sai T, Lu R, Modrusan Z, Hackney J, Ouyang W. NRROS negatively regulates the production of reactive oxygen species in phagocytes during host defense and autoimmunity. Nature. 2014 May 8;509(7499):235-9

Wu L, Li H, Luo X, Lu R, Ma Y, Wang R, Zhang, J, Yu H, Liu J. STAT3 activation in tumor cell-free lymph nodes predicts a poor prognosis for gastric cancer. Int J Clin Exp Pathol.2014 Feb 15;7(3)

Xin H, Lu R, Lee H, Zhang W, Zhang C, Deng J, Liu Y, Shen S, Wagner KU, Forman S, Jove R, Yu H. G-protein-coupled receptor agonist BV8/prokineticin-2 and STAT3 protein form a feed-forward loop in both normal and malignant myeloid cells.  J Biol Chem. 2013 May 10;288(19):13842-9.

Lu R, Pan H, Shively JE. CEACAM1 negatively regulates IL-1β production in LPS activated neutrophils by recruiting SHP-1 to a SYK-TLR4-CEACAM1 complex. PLoS Pathog. 2012;8(4).

Lu R, Kujawski M, Pan H, Shively JE. Tumor angiogenesis mediated by myeloid cells is negatively regulated by CEACAM1. Cancer Res. 2012 May 1;72(9):2239-50.

Lu R, Niesen MJ, Hu W, Vaidehi N, Shively JE. Lu R, Niesen MJ, Hu W, Vaidehi N, Shively JE. Interaction of actin with carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) receptor in liposomes is Ca2+ and phospholipid-dependent. J Biol Chem. 2011 Aug 5;286(31)

Abbvie Oncology Excellence Award, 2018

Abbvie Oncology Bistro Award, 2017

American Association of Immunologist Trainee Travel Award, 2011

Finalist, American Association for Cancer Research Travel Award, 2011

1st Place, annual City of Hope Poster Session, 2010

H.N. and Frances C. Berger Foundation Fellowship, 2008

Outstanding Student Scholarship, Tongji University, 2003-2007  

100 Best Students Award, Tongji University, 2005

Session Chair of Immuno-responsive workshop, Houston, Society for Immunotherapy of Cancer,  2019 

Session Chair of Immuno-responsive workshop, San Francisco,Society for Immunotherapy of Cancer, 2018               

Biomarkers for PD-1 blockade in lung cancer, Precision Lung Cancer Summit, Boston, 2018

Cancer Immune Resistance, Precision Blood Cancer Summit, San Francisco, 2017

The role of neutrophils in tumor metastasis, Tumor Microenvironments Research Program, School of Medicine, UC Davis, 2013

Structure& Function PILLARS, Dell Medical School