The importance of basic research

Research has classically been defined as either basic or applied. When we refer to basic research, it is carried out in a laboratory and seeks to identify the fundamental mechanisms that control biological processes. Basic research is crucial as it allows us to explore and test scientific knowledge in a very open way, for example, whether a potential future drug works “in vitro” or in animal models under controlled experimental conditions.

In our country, a large fraction of the basic research is carried out at the National Institutes of Health (NIH), an agency that is under the U.S. Department of Health and Human Services. At the NIH, one of the most prominent researchers is Paul E. Love, MD, PhD. He is professionally attributed as a senior investigator at NIH and the Head of an Immunology Laboratory in the Eunice Kennedy Shriver, National Institute of Child Health and Human Development (NICHD).

In his 31 years of experience, he has pursued primary basic research in the field of immunology and has made myriad contributions. Love also holds Residency/Board certification in Clinical Pathology, and completed a Fellowship in Human Genetics (NIH).

Love started working as an independent principal investigator at NIH in 1994 and was promoted to Senior Investigator in 1998. A constant theme of the Love-lab research has been investigating the role and function of multiple signal transducer modules called Immune-receptor-Tyrosine-based-Activation-Motifs (ITAMs) within the T Cell Antigen Receptor (TCR), the main activating receptor expressed by T cells (one of the classes of lymphocytes that are essential for clearing infectious pathogens and for tumor surveillance).

The TCR comprises six signal transducing subunits that contain a total of 10 ITAMs and the explanation for this peculiar signaling configuration has remained a subject of intensive research for many years. Love’s research has shown that one role of multiple ITAMs is to amplify TCR signals, and this is especially essential in the production of T cells and in the choice of alpha-beta/gamma-delta T cell lineage.

Applied (or translational) research utilizes discoveries identified through basic research to benefit human health, often by assisting in the treatment of diseases. A recent example of extraordinarily successful applied research is discovery in the mouse model of so-called checkpoint molecules that include Ctla4, PD-1 and PD-L1 that function to suppress or terminate T cell activation. It was shown in basic research experiments in mice that blockade of checkpoint molecules resulted in enhanced tumor killing by T cells. Application of this discovery to human medicine has revolutionized cancer therapy and contributed to the birth of an exciting new clinical field known as immunotherapy.

Two lines of basic research in Dr. Love’s lab have uncovered potential translational applications for human medicine. The first involves recent results suggesting that altering the sequence of TCR ITAMs may enhance T cell activity and function. These results indicate that ‘tailoring’ of the TCR signaling subunits can be used to modify TCRs so that they function better to induce tumor killing. The second is the identification of a class of molecules, called tuning molecules, that, similar to checkpoint proteins function to dampen TCR signals. Although identified in mice, tuning molecules are also expressed in human T cells and therefore represent attractive targets for human immunotherapy.

Importantly, Dr. Love relates that both of these discoveries were obtained through basic research aimed at gaining a better understanding of how T cells develop and acquire functional capability.