Upon graduation from UVA, she went directly to the National Cancer Institute in Frederick Maryland where she developed purification methods for Interferon alpha. It was this Interferon which was used in the first immune therapy treatment for hairy cell leukemia in 1986. In 1986-7, prior to enrolling in graduate school. she went to Upjohn Pharmaceuticals in Kalamazoo Michigan to develop production methods to insure biological materials manufactured using human blood products were free of contamination from HIV-1. Her PhD thesis defense entitled "Negative Regulation of HIV Expression in Monocytes" changed the paradigm for therapeutic treatment of HIV. For this work, she was awarded the graduate student of the year in 1991. In her thirty-five-year quest to understand and develop therapies for chronic diseases, she has co-authored seminal papers culminating at least a decade of research in each of four fields: immunology, natural products chemistry, epigenetics, and HIV/AIDs drug development.
In 2006, Dr. Mikovits became attracted to the plight of families with neuroimmune diseases including ME/CFS and Autism and was primarily responsible for demonstrating the relationship between environmentally acquired immune dysfunction, chronic inflammation and these diseases. Her pioneering work during a twenty year career at the National Cancer Institute includes the discovery of the modulation of DNA Methylation machinery by human retro viral infection and the development of the concept of inflammatory cytokines and chemokine signatures of infection and disease, which was first published in 1999, when Dr. Mikovits directed the Laboratory of Antiviral Drug Mechanisms in developing therapeutics and diagnostics for HIV/AIDS and AIDS associated malignancies. Therapies which are still standard of care twenty five years later and credited with saving millions of deaths from HIV/AIDS. In 2001, she moved back to industry where she directed the Cancer Biology program of EpiGenX Pharmaceuticals.
The company focused on the development multiplex diagnostic epigenetic and proteomics expression technologies for the prediction of Immune Related Adverse Events to chemotherapy in susceptible populations. In 2006 she co-founded and developed the first neuroimmune research institute dedicated to understanding the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and related illnesses. In five short years, she won more than 6 million dollars of NIH/DOD competitive funding in grants and contracts for this program. In 2009, Drs. Ruscetti and Mikovits' labs isolated for the first time a new family of human retroviruses then identified as XMRV. In 2012 it was learned XMRV was a contaminant of the Silverman lab and the XMRVs isolated were a new human exogenous and transmissible retrovirus family, which are strongly associated with neuroimmune disease and cancer. This new family of pathogenic human retroviruses is now called HGRV. Dr. Mikovits has co-authored more than 50 peer reviewed publications and book chapters and the book Plague.