Lei Xu

Associate Prof., Radiation Oncology

Xu Lab Research

Dr. Lei Xu's CV

The goals of my research team are to dissect mechanisms of disease progression and treatment resistance and to develop innovative strategies to enhance treatment efficacy and improve patient quality of life. My current research is focused on 3 diseases: 

Neurofibromatosis type 2: 

Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by non-malignant tumors grown on the hearing nerve, disrupting hearing and causing social impairment and clinical depression. The major unmet medical needs for NF2 are i) no drug is FDA-approved to treat the tumor or the associated hearing loss, and ii) the current standard treatment (surgery and radiation therapy) can further damage the nerve and aggravate hearing loss. Thus novel therapies with enhanced efficacy and reduced toxicity-related hearing loss are urgently needed.

The NF2 research is limited by i) the lack of orthotopic mouse models that reproduce tumor-induced hearing loss, ii) the lack of patient-derived cell lines, and iii) the lack of a targeted therapy that can simultaneously prevent hearing loss and control tumor growth. 

I have made several contributions to advance NF research and management. First, my group established novel mouse models that faithfully reproduce schwannoma-induced hearing loss and neurologic deficit  (PNAS 2015; Nature Protocol 2019, Experimental Neurology 2018, NeuroMethods 2021). In mice, the short length and small caliber of the vestibular nerves, and their encasement in the bony internal auditory canal pose significant technical challenges for orthotopic tumor implantation. My group developed a novel cerebellopontine angle (CPA) model that allows the measurement of hearing function in tumor-bearing mice. This model addresses a major bottleneck in the NF field and provides the NF research and clinical community with a robust and biologically relevant tool to explore new therapeutic targets to tackle this devastating disease. Then, using this new model, I discovered that cMET and angiotensin signaling are potential targets for NF2. Blockade of cMET signaling enhanced radiation efficacy and  reduced the radiation dose required for tumor control and thus limited radiation toxicity (PNAS 2018). Blockade of angiotensin signaling prevented tumor-induced hearing loss (Science Translational Medicine 2021). Based on our compelling data, the Department of Radiation Oncology at MGH has amended the current ongoing clinical trial (NCT01199978), to include 10 patients to be treated with losartan concurrently with fractionated proton therapy, with follow-up evaluations for hearing function.

Ovarian cancer:

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy. My ovarian cancer research is focused on: i) deciphering mechanisms of treatment-resistance, ii) identifying novel strategies to enhance treatment efficacy, and iii) reducing malignant ascites, which contribute to poor quality of life in patients with OvCa.

I discovered that normalizing the ovarian cancer tumor microenvironment by targeting TGF-b (Clinical Cancer Research 2011; PNAS 2012) and angiotensin signaling (PNAS 2019) not only enhances the delivery and efficacy of chemotherapy but also improves the diaphragm lymphatic vessel drainage function, leading to reduced ascites. These findings suggest a potential treatment to improve patients’ quality of life. In collaboration with MGH Gynecological Oncologists, I further demonstrated that in ~300 ovarian cancer patients treated at two Harvard Medical School-affiliated teaching hospitals (MGH and Brigham and Women’s Hospital) who received losartan survived 30 months longer than those taking other anti-hypertension drugs (PNAS 2019).


Schwannomatosis (SWN), a type of neurofibromatosis, is a rare genetic disordered characterized by multiple non-malignant schwannomas growing on the spine and peripheral nerves. Patients with SWN overwhelmingly present with intractable, debilitating chronic pain, severe enough to cause permanent disability.

Recognizing that one of the biggest challenges in finding a cure for SWN is the lack of clinically-relevant models, I collected patient samples and successfully established a biobank of patient-derived SWN cells. I also developed the first orthotopic patient-derived xenograft (PDX) SWN spine model in mice. Currently, using my novel PDX models, I’m investigating the etiology of tumor-induced pain response and testing the treatment efficacy of potential targets.

Lab News

Investigating Immunotherapy in Neurofibromatosis Type 2 Vestibular Schwannomas

Cerebellopontine Angle (CPA) Model: A Novel Tool for Investigating Immunotherapy in Neurofibromatosis Type 2 Vestibular Schwannomas

See the MGH press release here

Adding crizotinib to radiation therapy may help preserve hearing in patients with NF2

Cancer drug targets molecular pathway contributing to tumor progression, radiation-induced hearing loss

Xu Lab Team

Former Team Members

Cao, Jinghong
Chen, Jie, MD
Gao, Xing, MD
Liu, Jieqiong, M.S.
Roberge, Sylvie, MS
Sun, Yao
Wu, Limeng
Zhang, Na
Zhang, Yanling, MD
Zhao, Yanxia, Ph.D.
Zhao, Yingchao , MD
Zhu , Chao, MD

Xu Lab Careers

Postdoctoral Research Fellow

Investigator: Xu, Lei
Date Posted: 2024-04-07
The Xu Lab at the Steele Laboratories of Tumor Biology, Massachusetts General Hospital, Harvard Medical School, is seeking applications for Postdoctoral Research Fellow positions. The Steele Labs boast a diverse faculty and provide an engaging and supportive environment for cutting-edge interdisciplinary research. Multiple opportunities are available to delve into research areas including: i) Understanding the role of the abnormal tumor microenvironment in tumor progression, tumor-induced hearing loss, and tumor-induced pain response, ii) Developing and testing new therapeutic strategies that can simultaneously control tumor growth and improve patient quality of life, and iii) Translating these strategies from bench to bedside through multi-disciplinary clinical trials.
Candidates should demonstrate motivation, a solid academic background, a track record of peer-reviewed publications, and strong writing abilities. Salary will be commensurate with qualifications and experience, with additional funding for conferences and training seminars.
A PhD or MD/PhD is required. To apply, please send your CV, a statement outlining your career objectives, a summary of your most significant research accomplishments (300 words), and the contact information of three references to: lexu@mgh.harvard.edu.

Research technologist

Investigator: Xu, Lei
Date Posted: 2013-03-05
We are looking for a Research Technologist to join our Clinical Correlative Studies Core at the Edwin L. Steele Laboratory. The Technologist will have the primary responsibility of measuring protein concentration in blood and tissue samples from patients enrolled in clinical trials at the Massachusetts General Hospital.
Individuals must have a BSc degree, appropriate research experience, strong organizational, interpersonal, communication, and computer skills and be prepared to work in a dynamic team environment. Previous experience in enzyme-linked immuno-sorbent assay (ELISA), immunohistochemistry, flow cytometry, molecular biology and animal experimentation is preferred. Interested candidates should send a cover letter and resume to: </br> Lei Xu, M.D, Ph.D.</br> Edwin L. Steele Laboratory</br> Massachusetts General Hospital</br> 100 Blossom Street, Cox-7</br> Boston, MA 02114</br> E-mail: <a href="mailto:lei@steele.mgh.harvard.edu">lei@steele.mgh.harvard.edu</a>

Selected Publications (from total of 58)

Zhao Y, Liu P, Zhang N, Chen J, Landegger LD, Wu L, Zhao F, Zhao Y, Zhang Y, Zhang J, Fujita T, Stemmer-Rachamimov A, Ferraro GB, Liu H, Muzikansky A, Plotkin SR, Stankovic KM, Jain RK, Xu L
Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models.
Proc Natl Acad Sci U S A. 2018;115(9):E2077-E2084 - PMID: 29440379 - PMCID: PMC5834719 - DOI: 10.1073/pnas.1719966115
Askoxylakis V, Badeaux M, Roberge S, Batista A, Kirkpatrick N, Snuderl M, Amoozgar Z, Seano G, Ferraro GB, Chatterjee S, Xu L, Fukumura D, Duda DG, Jain RK
A cerebellar window for intravital imaging of normal and disease states in mice.
Nat Protoc. 2017;12(11):2251-2262 - PMID: 28981123 - PMCID: PMC5918134 - DOI: 10.1038/nprot.2017.101
Zhang N, Gao X, Zhao Y, Datta M, Liu P, Xu L
Rationally combining anti-VEGF therapy with radiation in NF2 schwannoma.
J Rare Dis Res Treat. 2017;1(2):51-55 - PMID: 28191549 - PMCID: PMC5300073
Peterson TE, Kirkpatrick ND, Huang Y, Farrar CT, Marijt KA, Kloepper J, Datta M, Amoozgar Z, Seano G, Jung K, Kamoun WS, Vardam T, Snuderl M, Goveia J, Chatterjee S, Batista A, Muzikansky A, Leow CC, Xu L, Batchelor TT, Duda DG, Fukumura D, Jain RK
Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages.
Proc Natl Acad Sci U S A. 2016;113(16):4470-5 - PMID: 27044097 - PMCID: PMC4843449 - DOI: 10.1073/pnas.1525349113
Kloepper J, Riedemann L, Amoozgar Z, Seano G, Susek K, Yu V, Dalvie N, Amelung RL, Datta M, Song JW, Askoxylakis V, Taylor JW, Lu-Emerson C, Batista A, Kirkpatrick ND, Jung K, Snuderl M, Muzikansky A, Stubenrauch KG, Krieter O, Wakimoto H, Xu L, Munn LL, Duda DG, Fukumura D, Batchelor TT, Jain RK
Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival.
Proc Natl Acad Sci U S A. 2016;113(16):4476-81 - PMID: 27044098 - PMCID: PMC4843473 - DOI: 10.1073/pnas.1525360113
Gao X, Zhao Y, Stemmer-Rachamimov AO, Liu H, Huang P, Chin S, Selig MK, Plotkin SR, Jain RK, Xu L
Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model.
Proc Natl Acad Sci U S A. 2015;112(47):14676-81 - PMID: 26554010 - PMCID: PMC4664377 - DOI: 10.1073/pnas.1512570112
Datta M, Via LE, Kamoun WS, Liu C, Chen W, Seano G, Weiner DM, Schimel D, England K, Martin JD, Gao X, Xu L, Barry CE, Jain RK
Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery.
Proc Natl Acad Sci U S A. 2015;112(6):1827-32 - PMID: 25624495 - PMCID: PMC4330784 - DOI: 10.1073/pnas.1424563112
Snuderl M, Batista A, Kirkpatrick ND, Ruiz de Almodovar C, Riedemann L, Walsh EC, Anolik R, Huang Y, Martin JD, Kamoun W, Knevels E, Schmidt T, Farrar CT, Vakoc BJ, Mohan N, Chung E, Roberge S, Peterson T, Bais C, Zhelyazkova BH, Yip S, Hasselblatt M, Rossig C, Niemeyer E, Ferrara N, Klagsbrun M, Duda DG, Fukumura D, Xu L, Carmeliet P, Jain RK
Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma.
Cell. 2013;152(5):1065-76 - PMID: 23452854 - PMCID: PMC3587980 - DOI: 10.1016/j.cell.2013.01.036
Liu J, Liao S, Diop-Frimpong B, Chen W, Goel S, Naxerova K, Ancukiewicz M, Boucher Y, Jain RK, Xu L
TGF-? blockade improves the distribution and efficacy of therapeutics in breast carcinoma by normalizing the tumor stroma.
Proc Natl Acad Sci U S A. 2012;109(41):16618-23 - PMID: 22996328 - PMCID: PMC3478596 - DOI: 10.1073/pnas.1117610109
Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK
Normalization of the vasculature for treatment of cancer and other diseases.
Physiol Rev. 2011;91(3):1071-121 - PMID: 21742796 - PMCID: PMC3258432 - DOI: 10.1152/physrev.00038.2010
Liu J, Liao S, Huang Y, Samuel R, Shi T, Naxerova K, Huang P, Kamoun W, Jain RK, Fukumura D, Xu L
PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer.
Clin Cancer Res. 2011;17(11):3638-48 - PMID: 21459800 - PMCID: PMC3107920 - DOI: 10.1158/1078-0432.CCR-10-2456
Duda DG, Kozin SV, Kirkpatrick ND, Xu L, Fukumura D, Jain RK
CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies?
Clin Cancer Res. 2011;17(8):2074-80 - PMID: 21349998 - PMCID: PMC3079023 - DOI: 10.1158/1078-0432.CCR-10-2636
Liao S, Liu J, Lin P, Shi T, Jain RK, Xu L
TGF-beta blockade controls ascites by preventing abnormalization of lymphatic vessels in orthotopic human ovarian carcinoma models.
Clin Cancer Res. 2011;17(6):1415-24 - PMID: 21278244 - PMCID: PMC3060297 - DOI: 10.1158/1078-0432.CCR-10-2429