Clark Jeffries’s research focuses on design and interpretation of assays of small RNAs as agents of signaling that may be causally upstream of many other types of biomarkers. Surveys of microRNAs in nuclear and cytoplasmic compartments of human neural progenitors have surprisingly revealed rich nuclear inventories as well as sequence patterns that seem characteristic of nuclear import. This implies that microRNAs might well be as important in regulation of nascent transcription as they are known to be in regulation of translation. Nuclear import and the small size of microRNAs (precluding some types of immune response), suggest their use at the very heart of gene regulation.
The active projects in the lab include:
- Computer analysis of small RNA sequencing data. Current technologies generate millions of “reads” of ~35 bases within which subsequences in random windows reflect RNA species. A pipeline specifically dedicated to understanding small RNAs has been created and in particular the problem of normalization between “lanes” has been solved (the same sample duplicated in two lanes can generate many times more reads in one than the other, so the goal is to find consistency within wildly different data). This program leads to selection of small RNAs that distinguish control from case. Then the same small RNAs can be probed by custom biochemical technologies that are far more reproducible and precise than gross sequencing data. The outcome can be new diagnostics of great value to patients and clinicians.
- A program with Prof. D. O. Perkins, MD, has centered on isolation of small stem cells from human blood. While difficult to control, the cells have been cultured in some cases for more than one year. Some have been treated with published protocols to differentiate them into much larger cells that are positive for neuronal markers. It seems possible that this technology might eventually allow generation of neuronal cells from living patients with mental illnesses, thus suggesting a variety of investigations of effects of medicines on a patient-specific basis. Presently selection of treatment for persons with prodromal psychosis is an important unsolved problem in psychiatry.
- In conjunction with Prof. W. K. Kaufmann, PhD, we have devised methods for “system identification,” traditionally an engineering exercise in which one goes from lab data to a model of a system that can be used to control a machine. Cell cycle data from cells responding to irradiation stress has been used to connect data to checkpoints for DNA damage in cells. This work pertains in the present instance to melanoma research but could be expanded to other types of assay data for stressed cells. The complex dynamic signatures of markers may indeed prove more informative than static signatures; this should include small RNA signatures.
- 1987-1992 Lecturer, Assistant Professor, Associate Professor, Professor of Mathematical Sciences, Clemson University, Clemson, SC
- 1998-2004 IBM Microelectronics Division, Senior Programmer, Research Triangle Park, NC: IBM Master Inventor 2003-2004
- 2005-present Research Scientist, Renaissance Computing Institute
- 2006-present Research Professor, University of North Carolina Eshelman School of Pharmacy
Developing assays for small RNAs in human cell lines and tissue samples and developing software to interpret small RNA signatures as diagnostics or theranostics.
Recent funded research
- 2U01MH082004-06A1 Contact PI / Project Leader: PERKINS, DIANA O.
Title: 5/9 PREDICTORS AND MECHANISMS OF CONVERSION TO PSYCHOSIS
Elucidating the underlying neurobiological processes in early psychosis will move us closer to targeted preventive interventions that have the potential to halt or ameliorate this neuropathological process. Jeffries’ role is interpretation of data from blood analyte assays (proteins, steroids, particles) and small RNA molecules thought to be pervasive regulators of gene expression.
- 5R34MH103834-02 Contact PI / Project Leader: PERKINS, DIANA O.
Title: IMPROVING CLINICIAN RECOGNITION OF EARLY PSYCHOSIS WITH AN INTERACTIVE ONLINE COURSE
In our first episode treatment program, OASIS, we propose to benchmark pathways to care to better determine reasons for treatment delay. Jeffries’ role is to devise algorithms to identify from data the combinations of crucial, common factors that immediately precede seeking medical attention.
- 3-U01-MH082004-05S1 Contact PI / Project Leader: PERKINS, DIANA O.
5/8 PREDICTORS AND MECHANISMS OF CONVERSION TO PSYCHOSIS
Using blood assays to predict risk of progression to schizophrenia
Role: Co-PI with Prof. D. Perkins, MD, Psychiatry Dept.
Overlap: overlaps with completed San Francisco Foundation work and precedes Administrative Supplement application.
- Jeffries CD, Perkins DO, Fournier M, Do KQ, Cuenod M, Khadimallah I, Domenici E, Addington J, Bearden CE, Cadenhead KS, Cannon TD8 Cornblatt BA, Mathalon DH, McGlashan TH, Seidman LJ, Tsuang M, Walker EF, Woods SW. Transl Psychiatry.Networks of blood proteins in the neuroimmunology of schizophrenia. 2018 Jun 6;8(1):112. doi: 10.1038/s41398-018-0158-y.
- Zheutlin AB, Jeffries CD, Perkins DO, Chung Y, Chekroud AM, Addington J, Bearden CE, Cadenhead KS, Cornblatt BA, Mathalon DH, McGlashan TH, Seidman LJ, Walker EF, Woods SW, Tsuang M, Cannon TD.The Role of microRNA Expression in Cortical Development During Conversion to Psychosis. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2017; PubMed [journal]PMID: 28186095
- Jeffries CD, Perkins DO, Chandler SD, Stark T, Yeo E, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, Mathalon DH, McGlashan TH, Seidman LJ, Walker EF, Woods SW, Glatt SJ, Tsuang M.Insights into psychosis risk from leukocyte microRNA expression. Translational psychiatry. 2016; 6(12):e981.
PubMed [journal]PMID: 27959328 PMCID: PMC5290334
- Cannon TD, Yu C, Addington J, Bearden CE, Cadenhead KS, Cornblatt BA, Heinssen R, Jeffries CD, Mathalon DH, McGlashan TH, Perkins DO, Seidman LJ, Tsuang MT, Walker EF, Woods SW, Kattan MW.An Individualized Risk Calculator for Research in Prodromal Psychosis. The American journal of psychiatry. 2016; 173(10):980-988. NIHMSID: NIHMS797083 PubMed [journal]PMID: 27363508 PMCID: PMC5048498
- Jeffries CD, Perkins DO. Reproducibility and Visual Inspection of Data. Biological psychiatry. 2016; 80(5):e33-5. PubMed [journal]PMID: 26774964
- Perkins DO, Jeffries CD, Cornblatt BA, Woods SW, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Heinssen R, Mathalon DH, Seidman LJ, Tsuang MT, Walker EF, McGlashan TH. Severity of thought disorder predicts psychosis in persons at clinical high-risk. Schizophrenia research. 2015; 169(1-3):169-77. NIHMSID: NIHMS729371 PubMed [journal]PMID: 26441004 PMCID: PMC4681584
- Perkins DO, Jeffries CD, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, Mathalon DH, McGlashan TH, Seidman LJ, Tsuang MT, Walker EF, Woods SW, Heinssen R.Towards a psychosis risk blood diagnostic for persons experiencing high-risk symptoms: preliminary results from the NAPLS project. Schizophrenia bulletin. 2015; 41(2):419-28. PubMed [journal]PMID: 25103207 PMCID: PMC4332942
- Cannon TD, Chung Y, He G, Sun D, Jacobson A, van Erp TG, McEwen S, Addington J, Bearden CE, Cadenhead K, Cornblatt B, Mathalon DH, McGlashan T, Perkins D, Jeffries C, Seidman LJ, Tsuang M, Walker E, Woods SW, Heinssen R; North American Prodrome Longitudinal Study Consortium. Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk. Biol Psychiatry. 2015 Jan 15;77(2):147-57.
- Perkins DO, Jeffries CD, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, Mathalon DH, McGlashan TH, Seidman LJ, Tsuang MT, Walker EF, Woods SW, Heinssen R. Towards a Psychosis Risk Blood Diagnostic for Persons Experiencing High-Risk Symptoms: Preliminary Results From the NAPLS Project. Schizophr Bull. 2014 Aug 6. pii: sbu099.
- Perkins DO, Jeffries C, Turaga V, Frelinger JK. Improved Methods to Isolate and Culture VSEL Stem Cells from Humans. International Society for Stem Cell Research 9th Annual Meeting, Toronto, June 15-18, 2011.
- Jeffries CD, Fried HM, Perkins DO. Nuclear and cytoplasmic localization of neural stem cell microRNAs. RNA. 2011 Apr;17(4):675-86.
- Jeffries CD, Perkins DO, Guan X. Gene processing control loops suggested by sequencing, splicing, and RNA folding. BMC Bioinformatics. 2010 Dec 20;11:602.