The evolving grammar of healthcare

The Clinical Biomarkers Discovery Laboratory at IIT Kharagpur is actively involved in using the newly emerged field of metabolomics, which is capable of providing biological end-point markers of the cellular processes that occur as a result of disease. The lab focuses on the use of metabolomics for comprehensive identification of disease biomarkers and understanding of the pathogenic mechanism underlying complex human diseases. Prof. Koel Chaudhury, who heads the lab, talks to the KGP Chronicle about how she has used the metabolomics approach to investigate women’s health, the progress her team has made and the future challenges.

Could you please give a brief summary of your research in the medical/life sciences domain?

The approach to illness and disease management has changed considerably with the evolution of medicine. In the past, medicine was strictly practiced according to the symptoms presented by the patient and was essentially based on the individual expertise of the physician, and thus was known as intuition medicine. Presently, medicine is based on the evidence produced by scientific research which also include the clinical trials, and is termed as evidence-based medicine. Most of the medical treatments today are designed for the average patient using the “one-size-fits-all” approach. Unfortunately, this type of treatment is seen to be very successful for some patients but not for others. In future, medicine is to be practiced according to algorithms that will take into consideration the patient’s characteristics, e.g. their genome, epigenetics, microbiomes, proteomes, metabolomes, environments and lifestyle to make diagnostic and therapeutic strategies precisely tailored to individual patients. It is envisioned that this will lead to the emergence of an effective P4 (predictive, preventive, personalized and participatory) healthcare system.

Our team uses the multi-omics approach including quantitative proteomics, NMR and mass spectrometry-based metabolomics to identify robust biomarkers in serum/urine/tissues/exhaled breath condensates/bronchoalveolar fluid which can assist in early disease prediction, identify disease sub-categories and predict individual disease risk. We also use ‘omics’-driven studies to enhance our understanding of the disease pathogenesis and monitor the therapeutic effect of drugs so that personalized therapeutic strategies targeting the underlying disease etiology can be developed.

What are the challenges that the research will help address?

Some of the clinical research questions our team is presently addressing using the ‘omics’ approach are listed below:

1. What is the underlying cause of unexplained recurrent miscarriage?
2. Can a set of biomarkers be developed for early prediction of spontaneous miscarriage (during first trimester of pregnancy, i.e. <12 weeks of gestation)?
3. Can Stage I endometriosis (usually exists without signs and symptoms) be diagnosed early?
4. What is the pharmacometabolomic effect of the drug dydrogesterone (a synthetic form of progesterone) in women with recurrent miscarriage?
5. Is Asthma-COPD Overlap (ACO) a new disease entity?
6. Can serum biomarkers replace the invasive right heart catheterization diagnostic procedure in patients with pulmonary hypertension?
7. Is differential diagnosis of the two granulomatous restrictive lung diseases, chronic hypersensitivity pneumonitis (HP) and advanced-stage sarcoidosis possible?
8. What is the effect of long-term doxycycline in improving COPD disease conditions?

In what stage of development is this research?

• Potential markers have been identified in the exploratory patient cohort of various diseases; validation of these promising markers is ongoing in a fresh cohort of patients
• Long term doxycycline as a possible therapeutic option for COPD is being explored
• Robust serum biomarkers have been identified in early stage endometriosis; fabrication of a minimally invasive multiplexed point-of-care diagnostic device for detection of these markers is underway

 What is the future of this research?

Our research is translational and interdisciplinary in nature. We have active collaboration with clinicians and faculty members of various departments within the Institute. The aim of our team is to carry out ‘omics’-driven translational health research which will provide the ideal platform to diagnose diseases early in a non/minimally invasive and cost-effective manner.

How will the upcoming Dr B.C. Roy Institute of Medical Science and Research hospital help this work?

• Large patient cohort is needed to generate error free data for biomarker discovery studies. The 400 bed hospital will provide the ideal set-up for such high-throughput data generation.
• Integration of metabolomic data with metabolic imaging (PET-CT) and molecular imaging will be possible, which will provide a more holistic view to the perturbations caused by the disease
• Discovering new drug targets, understanding drug mechanism of action at the proteome (pharmacoproteomics) and metabolome level (pharmacometabolomics), and the potential to investigate drug toxicity and resistance will become possible