Overview of the Tewari Lab
The Tewari lab is engaged in using tools from science and medicine to help build a more harmonious world. Our focus is on health, to make discoveries and create new  solutions that can facilitate healing for the body and mind. 

We use a wide range of tools in our work, spanning from artificial intelligence to cellular-molecular analyses to wearable devices and mobile apps to collect data from human beings in everyday life.
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 Our work is inherently interdisciplinary, bridging fields as diverse as biology, computer science and artificial intelligence, statistics, psychology, analytical chemistry, oncology, clinical medicine and even art, music, education, business and commercialization. By collaborating with researchers in each of these areas, we seek to understand how seemingly disparate aspects of physiology can be leveraged, facilitated by technology and A.I., to improve human outcomes and wellbeing.​

Defining biological and digital signatures of stress
  Stress is an unfortunate consequence of everyday life. Interventions to reduce stress are important for not only mental but also physical wellbeing. For patients, stress can negatively impact immune responses and affect treatment outcomes. With that being said, how can we measure and quantify stress? Researchers typically rely on self-reported surveys, but this measure is often highly subjective based on a patient’s own experiences. Together with the Madison lab in the Department of Psychology, the Tewari lab is testing the validity of wearable devices in detecting objective digital biomarkers that can be used to better understand and define stress.

Liquid and digital biomarkers for early detection and prediction of treatment complications and outcomes in CAR-T and BMT recipients
  For several years, the Tewari lab has been interested, first in bone marrow transplant (BMT), then in CAR-T cell therapy for the treatment of hematologic malignancies. Both BMT and CAR-T have risks associated with treatment, namely graft-versus-host disease (GvHD) and Cytokine Release Syndrome (CRS). Specifically, our interest is looking into liquid and digital biomarkers that can be used to detect these side effects earlier, and even predict the patients that are most likely to experience them.
  Our collaborators on this project include individuals from Departments of Pediatrics (Dr. Sung Choi, Dr. Gregory Yanik), Clinical Pharmacy (Dr. David Frame), and Internal Medicine Divisions of Hematology/Oncology (Dr. Marcus Geer, Dr. Monalisa Ghosh), and Rheumatology (Dr. Jason Knight, Dr. Yu [Ray] Zuo).
  Recently our team was among those selected for 2025 BOOST initiative, https://boldchallenges.umich.edu/boost/, for a project with Dr. Annelise Madison from the Department of Psychology, expanding our scope to include mental wellness and mindset to understand and develop interventions for any effects mental health can have on treatment outcomes.

Liquid Biopsies of Cancer for Early Treatment Monitoring and Detection
  “Liquid biopsies” utilize different, more easily obtainable, biofluids to try and detect DNA shed by tumor cells, referred to as cell-free tumor DNA (ctDNA). The Tewari lab, in collaboration with Dr. Paul Sweicicki, a head and neck cancer oncologist, and Dr. Chad Brenner, director of the head and neck cancer oncology program at the University of Michigan, have been working not only to enhance the sensitivity of a blood-based liquid biopsy, but also develop a new method using a urine-based test.
  One challenge within blood-based ctDNA assays is achieving enough sensitivity when tumor burden is low. To improve sensitivity of detection within HPV-associated head and neck cancers, we developed a multi-probe droplet digital PCR (ddPCR) assay. This assay has since been validated within a CLIA lab at UM, producing the MyHPVscore test, highlighting our research being taken from bench-to-bedside.
  An additional challenge for many patients is simply being able to access care facilities to receive such tests. We explored a urine-based liquid biopsy, where samples could be collected in the comfort of a patient's home and mailed to a testing lab. Urine DNA is more difficult to work with than DNA from blood, because as the DNA moves from the bloodstream, through the kidneys, only very short fragments are able to pass through. These short fragments would be missed by traditional PCR assays, which typically target fragments 100-150 bp in length. We developed an ultra-short ddPCR assay, capable of capturing and measuring these fragments for HPV-associated head and neck cancers.

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Using A.I. to improve mind-body health
  When you hear A.I., you may immediately think of large language model (LLM) chatbots, or artist-bots, maybe even more futuristic A.I. that exist within books and movies. In the Tewari Lab, when we think about A.I. we are thinking about the more advanced methods now available to us in machine learning and program-based problem solving. Can we provide a computer model, continuous, every changing information from a biological system, and have it generate the best sequence of actions to achieve desired results within that system?
  We are researching how we can utilize reinforcement learning to train A.I. models using wearable health data, to provide feedback to their human patient agents to help improve their health and wellness. This sort of learning could enable the development of individualized regimes of small activities (e.g. breathing activities, meditation exercises, nutritional reminders) that could generate larger returns on whole mind-body health.

Dietary interventions to mitigate treatment side effects through gut microbiome modulation
  Bone marrow transplants (BMT) can be a lifesaving treatment for many blood cancer patients. However, a complication of BMT can be Graft versus Host Disease (GvHD), where the donor immune cells from the BMT attack the patient's own body. GvHD can range from mild to life-threatening, so it isn't a complication to be taken lightly. To combat the onset and severity of GvHD, researchers are investigating an inexpensive and readily available potato starch food supplement as a simple dietary intervention.
  The Tewari Lab is a part of the large multi-lab research group conducting this research led by Dr. Mary Riwes. This group includes researchers from the Department of Earth & Environmental Sciences, Department of Molecular & Integrative Physiology, Department of Internal Medicine, Division of Infectious Disease, Department of Biostatistics and the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. Together, we are not only exploring whether this simple supplement can reduce GvHD, but also the mechanisms by which this can be achieved. This research study utilizes 16S sequencing to explore changes to patient's intestinal microbiome (Dr. Tom Schmidt), along with metabolomic analysis of blood and stool (Dr. Costas Lyssiotis) to better understand how potato starch can promote certain microbial populations and the beneficial metabolites they produce.

More information about this study can be found in:
​Nature Medicine publication: "Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation"
ClinicalTrials.gov: Dietary Manipulation of the Microbiome-metabolomic Axis for Mitigating GVHD in Allo HCT Patients

Precision measurements for increased biomarker sensitivity
Precision measurements of the smallest of biologic molecules (nucleic acids and proteins) are often necessary for early disease detection. Technologies like PCR are able to assist through amplification of targets of interest, but can result in artifacts and are limited to nucleic acids. The Tewari lab has collaborated with Dr. Nils Walter and Dr. Alexander Johnson-Buck in the Department of Chemistry, in the development of new technologies for precision biomarker measurement. 
SiMREPS …. is a method of detecting and quantifying microRNA within biological liquids using kinetic fingerprinting. During the study, we found SiMREPS capable of detecting abnormal concentrations of miRNA associated with prostate cancer in a simulated test. Because this method does not require the amplification of RNA concentrations, it is both much quicker and more accurate at lower concentrations in detecting miRNA biomarkers. 
Bio-SCOPE…combines kinetic and chromatic fingerprinting to detect a varied array of biomarkers, including miRNAs, mutant DNA, and proteins. As a multiplexed detection system, Bio-SCOPE is time-efficient, comprehensive, and more sensitive to lower concentrations of a target molecule amongst higher concentrations of nontarget molecules in a biological liquid.
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