Laura Manuelidis

Laura Manuelidis is a physician and neuropathologist at Yale University.
Career.
Dr. Manuelidis earned her B.A. degree from Sarah Lawrence College, where she studied poetry, and her M.D. from Yale Medical School. She is head of the section of Neuropathology in the department of Surgery at Yale. She is also on the faculty of Neurosciences and Virology. Her major contributions include the discovery of complex repeated DNAs at centromeres and on chromosome arms (LINES) in large Giemsa bands that define tissue specific genes. She also illuminated the compact 3-D organization and structure of individual chromosomes in the interphase nucleus (not spaghetti-like chromatin) by developing high resolution non-isotopic in-situ hybridization, and further demonstrated positional specificity in different functional cell types, such as neurons and glia 
Achievements.
The Manuelidis lab was the first to serially transmit any form of human Creutzfeldt–Jakob disease (CJD) to small rodents. This made it possible to elucidate fundamental mechanisms of infection, including infectious agent uptake and spread by myeloid cells of the blood, lack of maternal transmission, and major strain differences of human Transmissible Spongiform Encephalopathy (TSE) agents such as sporadic CJD, kuru of New Guinea, bovine-linked vCJD in the UK, and Asiatic CJD. Her development of monotypic tissue cultures infected by many different human and sheep scrapie TSE strains along with rapid quantitative assays of infectivity showed that PrP band patterns are cell-type dependent and not specific for the agent-strain. TSE agents replicate every 24 hrs in culture in contrast to their slow replication in brain that has many complex host immune system controls.
Prion Hypothesis.
She has challenged the dominant explanation that the host prion protein (PrP), without any nucleic acid, is the causal infectious agent in TSEs. The prion hypothesis was put forth by Stanley B. Prusiner, who won the 1997 Nobel Prize in Physiology or Medicine. In contrast to the amyloid or "infectious form of host PrP", Manuelidis and colleagues showed that infectious CJD brain particles separated from most prion protein with a homogeneous viral density and size, and disruption of CJD nucleic acid-protein complexes destroys infectivity. Comparable 25 nm particles were identified within CJD and scrapie infected cell cultures, but not in uninfected controls. As with 25 nm brain particles, the culture particles did not bind PrP antibodies.
Manuelidis stated that, "Although much work remains to be done, there is a reasonable possibility these are the long sought viral particles that cause transmissible spongiform encephalopathies. The [prion] is probably not infectious, but is a pathological result [of] an infectious virus binding to this host protein.". Much additional recent evidence points to an exogenous source of infectious TSE agents and the claim that recombinant PrP can be made infectious has not been reproduced. In fact, one can remove all detectable forms of PrP from infectious brain particles, yet the brain particles retain their high infectivity. Thus, PrP may not be an integral component of the infectious agent, but instead a host susceptibility factor. Additionally, nucleases that have no effect on PrP are able to obliterate particle-associated nucleic acids and destroy >99% of their infectivity. These findings suggest that TSE agents are viruses that require protected genetic material to infect their hosts. Although novel circular SPHINX DNAs from the microbiome were identified in isolated infectious particles, their role in infection and/or disease is not yet clear.