Life Sciences

Dr. Singh has an extensive scientific background in studying molecular mechanisms associated with HIV infection and pathogenesis, 基因组印记, 分子生物学和小鼠疾病模型. Dr. Singh’s research interests include understanding the underlying molecular mechanisms involved in- i) HIV associated 神经障碍, ii) HIV latency, 病毒感染诱发发育缺陷. 下面列出了他实验室的两个主要项目.

项目1:艾滋病毒相关合并症(神经系统疾病); Introduction of combined antiretroviral therapy (cART) has successfully impeded the development of Acquired Immunodeficiency Syndrome (AIDS) and people infected with HIV are living near-normal life span. Unfortunately, various reasons, 包括cART毒性和低, 尽管是持久的病毒宿主, put these individuals at a higher risk of developing age associated secondary disorders such as cardiovascular disease, 神经障碍, 肾脏疾病和癌症. Dr. Singh’s recent studies have established that HIV can disrupt Blood-Brain-Barrier (BBB) integrity by specifically downregulating Sonic hedgehog (Shh) signaling in brain. BBB disruption is the key event leading to onset of neuroinflammation fueled by the infiltration of HIV infected/activated immune cells in the brain tissue. Dr. Singh’s ongoing research is focused at acquiring a deeper understanding of the roles played by Shh signaling in regulating brain homeostasis specifically in response to viral infection. This line of work presents potential opportunities to design adjunct therapeutic strategies to alleviate viral infection (e.g. HIV、HTLV、HSV、JC病毒和Zika病毒)诱导的神经发病机制.

项目2:HIV治愈研究:消除病毒库; The biggest obstacle in achieving cure for HIV is the latent viral reservoirs which are established very early following the infection. There is an inherent heterogeneity among HIV-1 latent reservoirs presumably due to multiple epigenetic mechanisms that drive viral latency, 细胞寿命和宿主免疫反应的调节. 正是由于这个原因，大多数潜伏期逆转剂(LRAs), 哪些在体外效果很好, 是否发现在体内影响病毒储存库时效率低下. Hence, 确定共同的下游目标非常重要, which are capable of modulating multiple cellular processes in various cell types - long non-coding RNAs (lncRNAs) are among such effectors. Dr. Singh has initiated a novel line of investigation to study the establishment and maintenance of latency orchestrated by multiple partners, including a select class of noncoding RNAs and intrinsic factors of innate immune response that might be working synergistically to keep the integrated provirus in a repressed state. This investigation is supported by exciting preliminary research that was funded by Center for AIDS Research (CFAR, 罗彻斯特大学(University of Rochester)的一项试点奖励. Singh. Successful completion of this study will identify novel targets and pave the way towards HIV cure by ‘Shock and Kill” approach to eliminate latent reservoir.

RESEARCH GRANTS

1. NIH R15 (AREA) Award (R15AI165295-01A1; 2022-2025; $495,000). 研究RNA聚合酶III驱动的机制调节HIV潜伏期. (Role: PI)
2. 乔治华盛顿大学NIH次级奖(2021-2022)(96美元),血小板介导的对HIV的神经炎症反应. (角色:公共卫生服务中心主任)
3. 马里兰大学医学院艾滋病研究中心试点奖(2018-2019)(30美元),000): Targeting Polymerase III transcribed long noncoding RNAs for reactivation of HIV latency. (Role: PI)
4. Micro grant (2016) from CFAR at URMC ($2500) to perform microarray: Identification of the long noncoding RNAs (lncRNAs) required for establishment and maintenance of HIV latency. (Role: PI)

科学的服务:

• 美国病毒学学会会员(自2021年起)
• 美国微生物学会会员(自2020年起)
• President Elect, American Society of Microbiologists, Easter New York (ENYASM) Chapter
• 传染病领域科学报告编委会成员.
• 科学报告的特别审稿人, PLOS One, 国际神经炎症与生物医学研究杂志.
• 神经免疫药理学学会(SNIP)成员(2013年至今).
• 2015-2018年SNIP早期职业研究者奖(ECITA)委员会成员.

选定的出版物

• Khan Irfan, Worrad Arthur, Singh Meera, Maggirwar Sanjay， Singh Vir*. Human Immunodeficiency Virus-1 exerts its neurotoxic effects by downregulating Sonic hedgehog signaling. 《全球十大赌博靠谱的平台》，2022年2月18日. doi: 10.1007/s13365-022-01061-8.
• Monocytes complexed to platelets differentiate into functionally defective dendritic cells. 米拉·辛格，苏曼·苏旺纳科恩，西德尼·辛普森，艾米丽·韦伯， Vir Singh， Pawel Kalinski, Sanjay Maggirwar，白细胞生物学杂志，2020年7月14日.
• A novel mechanism of microvesicle regulation by the anti-viral protein tetherin during HIV infection. 艾米丽·韦伯，米拉·辛格， Vir Singh， Joseph Jackson, Sara Ture, sumann Suwunnakorn, Craig Morrell, Sanjay Maggirwar. J. Am Heart Assoc. 2020年9月,9 (17):e015998.
• Ayse Kizilyer, Meera V Singh， Vir B Singh詹姆斯·帕里斯、桑杰·B·马格瓦尔(2018). Inhibition of Tropomyosin Receptor Kinase A Signaling Negatively Regulates Megakaryopoiesis and induces Thrombopoiesis. Sci Rep. 2019年2月26日;9(1):2781. doi: 10.1038/s41598-019-39385-x.
• Singh VB*， Singh MV, Piekna-Przybylska D, Gorantla S, Poluektova LY, Maggirwar SB. Sonic Hedgehog mimetic prevents leukocyte infiltration into the CNS during acute HIV infection. Sci Rep. 2017年8月29日;7 (1):9578. Doi: 10.1038/s41598-017-10241-0. *通讯作者
• Vir B. Singh， Sirinapa Sribenja, Kayla E. 克里斯托弗·威尔逊. Attwood, Joanna C. 希尔曼，希尔帕·帕塔克和迈克尔·J·希金斯. Blocked transcription through KvDMR1results in absence of methylation and gene silencing resembling Beckwith-Wiedmann syndrome. Development 2017 May 15; 144 (10) :1820-1830. doi: 10.1242/dev.145136. Epub 2017 Apr 20.
• Singh MV, Weber EA， Singh VB， Stirpe NE, Maggirwar SB. Preventive and therapeutic challenges in combating Zika virus infection: are we getting any closer? J Neurovirol. 2017 Jan 23.
• 杰克逊JW辛格MV Singh VB， Jones LD, Davidson GA, Ture S, Morrell CN, Schifitto G, Maggirwar SB. Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis. PLoS One. 2016, June 6; 11(6).
• Vir B. Singh*, Meera V. Singh, Santhi Gorantla, Larisa Y. 波鲁克托娃，桑贾伊·B. Maggirwar (2016). Smoothened agonist reduces Human Immunodeficiency Virus type-1- induced blood brain barrier breakdown in humanized mice. Sci Rep. 2016 May 31; 6:26876. doi: 10.1038/srep26876. *通讯作者
• Singh M.V., Donna D.C., Jackson J.W., Singh V.B., Silva J., Ramirez S.H. Maggirwar S.B. Characterization of Platelet-Monocyte Complexes in HIV-1-Infected Individuals: Possible Role in HIV-Associated Neuroinflammation. J. Immunol. 2014年，第192卷(10). Page 4674-84.

出版作品完整列表:  http://www.ncbi.nlm.nih.gov/myncbi/vir.singh.1/bibliography/public/

会议和演讲

• Imran Jamal, Anisha Paudel, Landon Thompson, Michel Abdelmalek, Irfan Khan， Vir B. Singh*. Activation of NRF-2 signaling inhibits the reactivation of HIV-1 in latently infected cells. Keystone Symposium on Viral Immunity: Basic Mechanisms and Therapeutic Applications (June 29-July 2nd, 2022, Keystone, CO).
• Irfan A. khan, Arthur H. Worrad, Meera V. Singh, Sanjay B. Maggirwar, Vir B. Singh. Human Immunodeficiency Virus-1 Tat exerts its neurotoxic effects by downregulating Sonic Hedgehog signaling. 第四届国际神经病学和脑部疾病会议. 2021年9-11日，虚拟活动). (口头报告)
• Irfan A. khan, Arthur H. Worrad, Meera V. Singh, Sanjay B. Maggirwar, Vir B. Singh*. Human Immunodeficiency Virus-1 Tat exerts its neurotoxic effects by downregulating Sonic Hedgehog signaling. ENYASM秋季研讨会(2021年10月1日，虚拟活动). (口头报告)
• Vir B Singh, Meera V Singh, Emily A Weber, Robert A Lopez-Astacio, Danielle M Reid, Sanjay B Maggirwar. HIV-Tat induces its Neurotoxic Effects by Downregulation of Sonic Hedgehog signaling in Brain. HIV & Aging conference, Emory School of Nursing (11-12th April 2019), Atlanta, GA, USA (Oral Presentation).
• Singh V B， Singh M V, Jones L D, Shanthi G, Poluektova L Y, Maggirwar S B. Sonic hedgehog信号在HIV-1感染的人源化小鼠中赋予神经保护作用. 神经免疫药理学学会第21届年会，2015年4月22-25日. 迈阿密，佛罗里达州，美国(口头报告).