Research group - Ujjwal Neogi

Towards precision medicine for people living with HIV (PLHIV)?
The Neogi lab work towards unraveling the mechanism of inflamm-aging in people living with HIV (PLHIV) on successful therapy to identify biomarkers for potential future clinical intervention and understand the mechanisms of natural immune control in HIV-1 infection using multi-omics system biology approach amalgamating with in vitro and ex vivo experimental assays. 

Research Group Leader

Ujjwal Neogi, Senior Researcher

I obtained my doctoral degree from Department of Medicine Huddinge, Karolinska Institutet (KI) in 2013. My research expertise is in virology, molecular biology, high-throughput sequencing and translational research. My research focuses on bedside to bench and back approach using well defined clinical material and ex vivo immunological assays amalgamating the translational research to understand the host and viral factors associated with disease progression and control in HIV-1. I intend to use high-throughput multi-omics integrated trans-omics approach to find out the mechanism of natural immune control of HIV-1 replication followed by deep insight in the individual pathways. My research interest also includes evaluation of the gut-microbiome metabolome axis and it’s role in disease progression and treatment efficacy.

Theme 1- Inflamm-aging and metabolism:

Although mortality is prevented and/or delayed because of effective combination antiretroviral therapy (cART), people living with HIV (PLHIV) need to take medication life-long. The cART has also shifted the spectrum of morbidity towards non-infectious complications such as cardiovascular and neurocognitive diseases that appear at an earlier age in people living with HIV (PLHIV) than in HIV-uninfected individuals. Inflamm-aging, i.e., human aging characterized by a chronic, low-grade systemic inflammation is a highly significant risk factor for both morbidity and mortality in older adults. During cART, HIV persists in a rare population of long-living, latently infected cells that can contribute to an inflammatory-like state. Our group aims to understand the genetic, cellular, and molecular mechanisms of inflamm-aging in PLHIV on successful long-term treatment. We are applying high-throughput multi-omics technologies (e.g., epigenomics, transcriptomics, proteomics, and metabolomics), along with in vitro and ex vivo experimental methods that help bridge the gap between genotype and phenotype and to understand how it regulates inflamm-aging and age-related diseases in PLHIV. Our studies can, therefore, provide possibilities to therapeutically target the inflamm-aging process through metabolic interference, thus allowing more individualized care.

Theme 2- Mechanism of immune control of HIV-1 replication:

Our lab is also aiming to understand the mechanisms of immune control in HIV-1 infection, focusing in particular on HIV-1 infected individuals called Elite Controllers (EC) who control HIV infection spontaneously without the need for medication. EC is a group of HIV-1 positive individuals who control viral replication and restrained progression to immunodeficiency, without any antiretroviral therapy for a longer duration of time. We will systemically perform the novel high-throughput transcriptomics, proteomics, microbiome, and metabolomics data with the aim of identifying the mechanistic insights of the novel biomarkers of natural immune control. Finally, we want to map the cellular pathways related to cell surface receptor signaling, immune checkpoint and death receptor signaling pathway that are significantly modulated in HIV-1 immune control and it’s cross-talk with the HIV-1 viruses. Systemic understanding the unique gene and proteome profiling and immunological characteristics of EC will predict a frame of reference for what may be required in clinical intervention strategies to induce immune control of HIV-1. Thus, these studies aim to generate immense knowledge that can be translated into the future development of functional HIV-cure including therapeutic vaccine strategies.

Theme 3- HIV-1 drug resistance and treatment response

Despite successful cART, resistance to a key HIV drug is common worldwide. Our study also aims to understand the subtype-specific differences in the evolution of drug resistance and treatment response. Using several cohorts from Europe, Asia, and Africa, we try to understand the role of naturally occurring polymorphisms in the drug target sites of cART drugs of class reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors in treatment response. We use technologies like deep-profiling by high throughput sequencing, in vitro and ex vivo phenotypic assays, biochemical and structural biology assays.  

Group members

Maike Sperk, PhD Student

I completed my master degree in Molecular Medicine from Tuebingen University, Germany (January 2018). In my master thesis, I focused on proteomics as well as cell biology and I will pursue these fields in a deeper way during my Ph.D. In particular, in my doctoral studies, I aim to perform immuno-proteomics research to map the intracellular pathways that are significantly modulated in HIV-1 immune control in Elite Controllers. I use high throughput techniques such as mass spectrometry, proximity extension assay, FACS, confocal microscopy, etc. My primary interests are death receptor signaling and stimulatory immune checkpoint molecules, and their roles in HIV-1 disease progression.

Anoop T Ambikan, PhD Student

I got my Master’s Degree in Bioinformatics from Amrita School of Biotechnology, India in 2012 and had more than two years experience as Bioinformatics Programmer, at SciGenome Pvt Ltd.  My doctoral studies aim at dealing with bioinformatics analysis of various kinds of "omics data" like transcriptome, proteome, microbiome and metabolome data related to HIV research. I am working to develop a simplified and efficient pipeline to integrate multi-omics data to draw a clinically relevant inference with reduced manual effort

Duncan T Njenda, PhD Student

Joint Karolinska Institutet- Stellenbosch University Double Degree program.

I obtained my master degree in Medical Virology, Stellenbosch University, South Africa. My expertise is in virology and molecular biology. My Ph.D. program is to identify resistance mechanisms against protease inhibitors in South African HIV-1C patients’ high throughput system biology approach. I aim to integrate molecular biology, biochemistry, virology and structural biology to understand the resistance mechanisms. 

Xi Chen, PhD Student

I finished my master degree in immunology, Sun Yat-sen University, China (July 2018). During my master study, my research direction was towards finding an effective latency reversing agent (LRA) and cytotoxic T-lymphocytes’ (CTLs’) influence on the establishment and maintenance of HIV-1 latent reservoir. In my doctoral study, I aim to understand the role of mammalian target of rapamycin, also known as the mechanistic target of rapamycin (mTOR) pathway in HIV-1 latency and inflamm-aging in people living with HIV (PLHIV) using proteomics, metabolomics, and immunological studies. I am the recipient of China Govt China Scholarship Council (CSC) funding.

Naveen Reddy Muppani, Visiting Researcher

I received a Ph.D. at Karolinska Institutet in 2013, and worked as a postdoc at Wright State University, USA 2014-2016. I held a researcher position at the Uppsala University during 2017-2018. I have expertise in transcription factors mediated regulation of gene and microRNA expressions governing cell life and death.

Currently, I am developing multiplexed assays for simultaneous detection of proteins and nucleic acids in situ and in solution that are exhibiting increased sensitivity and specificity. My aim is to develop multiplexed methods which employ routinely available laboratory instruments and establish them at limited recourse laboratory settings.

Ashokkumar Manickam, PostDoc

I submitted my Ph.D. at the Department of HIV/AIDS, National Institute for Research in Tuberculosis (affiliated to University of Madras, Chennai), India on understanding the transmitted/founder HIV-1 viruses in the establishment of the infection. Here, I have joined in Ujjwal Neogi’s group, LabMed as a Postdoctoral fellow to carry out the studies that involve in understanding the molecular mechanisms and the role of the HIV-1 latent reservoir in inflamm-aging in people living with HIV (PLHIV) who are on long-term successful therpay.

Associated members

Robert Van Domselaar, Karolinska Institutet

Wang Zhang, Karolinska Institutet

Sara Svensson Akusjärvi, Karolinska Institutet

Shambhu Prasad Ganeshappa Aralaguppe, Karolinska Institutet

Kamlendra Singh, PhD, University of Missouri, US

Hemalatha Babu,  PhD Student, National Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, India

Techniques

High throughput sequencing, epigenetics, transcriptomics, proteomics, metabolomics, RNAscope, miRNA profiling

Collaborations

Dr. Luke Elisabeth Hanna, National Institute for Research in Tuberculosis, India

Prof. Andrew D Badley, Mayo Clinic, US

Prof. Susan Engelbrecht and Dr. Graeme Jacobs, Stellenbosch University, South Africa

Asso. Prof. Aman Russom, KTH Royal Institute of Technology, Sweden

Prof. Stefan Sarafianos, Emory University, US

Prof. Thomas Klimkait, University of Basel, Switzerland

Prof. Ulf Landgren, Uppsala University, Sweden

Funding

Swedish Research Council-Establishment Grant (2017-01330)

Harald and Greta Jeansson Foundation (JS2016-0185)

Karolinska Institutet Doctoral Student Funding (KID2015-154)

Karolinska Institutet Research Foundation Grants special grant for Young Scientist

Swedish Physicians against AIDS Foundation (Fob20170004/Fob2015-009)

Jonas Söderquist’s Stipendium for Experimental Virology and Immunology Research-2016 (Award)

US National Institute of Health (R01 GM118012-01) (Site-PI)

Swedish Research Council (2015-05914/2017- 05848) (Co-I)

Stockholm County Council, ALF-Project Funding Medicine (Ref#20160074) (Co-I)

Selected publications

Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
Ashokkumar M, Aralaguppe S, Tripathy S, Hanna L, Neogi U
J. Virol. 2018 05;92(9):

Transcriptomics and Targeted Proteomics Analysis to Gain Insights Into the Immune-control Mechanisms of HIV-1 Infected Elite Controllers.
Zhang W, Ambikan A, Sperk M, van Domselaar R, Nowak P, Noyan K, et al
EBioMedicine 2018 Jan;27():40-50

Phenotypic co-receptor tropism and Maraviroc sensitivity in HIV-1 subtype C from East Africa.
Siddik A, Haas A, Rahman M, Aralaguppe S, Amogne W, Bader J, et al
Sci Rep 2018 Feb;8(1):2363

Plasma soluble factor following two decades prolonged suppressive antiretroviral therapy in HIV-1-positive males: A cross-sectional study.
Sperk M, Zhang W, Nowak P, Neogi U
Medicine (Baltimore) 2018 Feb;97(5):e9759

Virological failure in patients with HIV-1 subtype C receiving antiretroviral therapy: an analysis of a prospective national cohort in Sweden.
Häggblom A, Svedhem V, Singh K, Sönnerborg A, Neogi U
Lancet HIV 2016 Apr;3(4):e166-74

Genomics