School of Medicine

Wayne State University School of Medicine

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Robert Akins
Title
Professor
Phone
313-577-0419
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Education:
Ph.D. Microbiology, Ohio State University, 1981

Activities:
Director, Master's Program MIB 

Research:
Microbiomics, fungal exosomes, molecular diagnostics, antifungal resistance

 

Interests

Vaginal microbiome in health and disease
The vaginal mucosa is composed of perhaps hundreds of bacterial species, many of which have not yet been cultured or identified. These populations shift for unknown reasons, from healthy compositions to those that cause disease such as bacterial vaginosis (BV). Different profiles of species lead to complications ranging from recurrence, failed response to treatment, or risk of pre-term birth. Our microbiomics project seeks to characterize and count species, to describe the dynamics of populations as they transition to disease, and to identify species or groups that pose the highest risk for complications, including those that impose greater risks for cervical cancer. We are testing models for causes of the microbial progression from BV to cure to recurrence. We are developing a BV diagnositic and prognostic device.

Fungal exosomes
Extracellular vesicles (EV’s) and a subgroup of these called exosomes are subjects of a relatively new field of study that have cause a rethinking of how cells communicate and promote disease. Cells across all kingdoms generate EV’s, and they play important yet not fully understood roles in cancer progression, infectious diseases, such as tuberculosis, malaria, and mycoses, neurodegenerative disease, and many other areas. Candida, a major fungal pathogen, has recently been shown to generate EV’s with discrete protein and RNA cargo that may influence immune cells and survival in model systems. Their clinical potential for fungal infections is vast, because they may be produced in much larger numbers than the fungal cells themselves, because they likely disseminate to blood, saliva, urine for non-invasive detection, because they may carry RNA or protein cargo that distinguishes colonization from infection and possibly antifungal resistance information, and because they may be engineered to target antifungal therapies or for vaccine development. We are asking which stress conditions generate EV’s, whether they impact on the phenotype of other cells in the population, what protein and RNA cargo they carry, with the goal of defining diagnostic targets, and to begin testing whether vesicles in this fraction can be loaded with antifungals for targeted delivery to fungal cells.


Molecular fungal diagnostics
Fungal infections are prevalent and prone to recurrence (vaginal) or have high morbidity (systemic). Their diagnosis by conventional culture is a problem, due to poor culture efficiency, slow growth rates, and low titer, so that diagnosis often occurs too late for effective treatment. We are developing and are validating molecular tools for their high throughput, quantitative identification directly from samples.


Antifungal drug resistance in Candida albicans
As a eukaryote, this opportunistic yeast pathogen is resourceful and diverse in finding ways to evade inhibition by antifungal agents. These include mutation in target genes, mutational or regulatory activation of target and compensatory pathways, drug efflux, and unknown mechanisms. We are looking at mechanism by which this yeast induces high frequency loss of heterozygosity and an adaptive mechanism. We developed an overexpression system for identification of genes that alter antifungal susceptibility and are inventorying these genes and their effects by RT-qPCR and microarray.

Research Areas

  • Vaginal microbiome in health and disease
  • Molecular fungal diagnostics
  • Antifungal drug resistance in Candida albicans
     

Patents
U.S. Provisional Patent Application WSU 13-1141, Docket 2066728-00076 entitled METHODS AND KITS TO ASSESS HEALTH OF THE VAGINAL MICROBIOME

 

Publications

1. Sobel JD, Akins RA. 2015. The Role of PCR in the Diagnosis of Candida Vulvovaginitis-a New Gold Standard? Current infectious disease reports 17:488.
2. Aguin TJ, Akins RA, Sobel JD. 2014. High-dose vaginal metronidazole for recurrent bacterial vaginosis--a pilot study. Journal of lower genital tract disease 18:156-161.
3. Aguin T, Akins RA, Sobel JD. 2014. High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study. Sexually transmitted diseases 41:290-291.
4. Lambert JA, Kalra A, Dodge CT, John S, Sobel JD, Akins RA. 2013. Novel PCR-based methods enhance characterization of vaginal microbiota in a bacterial vaginosis patient before and after treatment. Applied and environmental microbiology 79:4181-4185.
5. Lambert JA, John S, Sobel JD, Akins RA. 2013. Longitudinal analysis of vaginal microbiome dynamics in women with recurrent bacterial vaginosis: recognition of the conversion process. PloS one 8:e82599.
6. Mandviwala T, Shinde R, Kalra A, Sobel JD, Akins RA. 2010. High-throughput identification and quantification of Candida species using high resolution derivative melt analysis of panfungal amplicons. The Journal of molecular diagnostics : JMD 12:91-101.
7. Akins RA. 2005. An update on antifungal targets and mechanisms of resistance in Candida albicans. Medical mycology 43:285-318.
8. Moosa MY, Sobel JD, Elhalis H, Du W, Akins RA. 2004. Fungicidal activity of fluconazole against Candida albicans in a synthetic vagina-simulative medium. Antimicrobial agents and chemotherapy 48:161-167.
9. Du W, Coaker M, Sobel JD, Akins RA. 2004. Shuttle vectors for Candida albicans: control of plasmid copy number and elevated expression of cloned genes. Current genetics 45:390-398.
10. Vazquez JA, Arganoza MT, Boikov D, Akins RA, Vaishampayan JK. 2000. In vitro susceptibilities of Candida and Aspergillus species to Melaleuca alternafolia (tea tree) oil. Revista iberoamericana de micologia 17:60-63.
11. Hidalgo JA, Alangaden GJ, Eliott D, Akins RA, Puklin J, Abrams G, Vazquez JA. 2000. Fungal endophthalmitis diagnosis by detection of Candida albicans DNA in intraocular fluid by use of a species-specific polymerase chain reaction assay. The Journal of infectious diseases 181:1198-1201.
12. Yoon SA, Vazquez JA, Steffan PE, Sobel JD, Akins RA. 1999. High-frequency, in vitro reversible switching of Candida lusitaniae clinical isolates from amphotericin B susceptibility to resistance. Antimicrobial agents and chemotherapy 43:836-845.
13. Vazquez JA, Arganoza MT, Boikov D, Yoon S, Sobel JD, Akins RA. 1998. Stable phenotypic resistance of Candida species to amphotericin B conferred by preexposure to subinhibitory levels of azoles. Journal of clinical microbiology 36:2690-2695.
14. Steffan P, Vazquez JA, Boikov D, Xu C, Sobel JD, Akins RA. 1997. Identification of Candida species by randomly amplified polymorphic DNA fingerprinting of colony lysates. Journal of clinical microbiology 35:2031-2039.
15. Vazquez JA, Arganoza MT, Vaishampayan JK, Akins RA. 1996. In vitro interaction between amphotericin B and azoles in Candida albicans. Antimicrobial agents and chemotherapy 40:2511-2516.
16. Min J, Arganoza MT, Ohrnberger J, Xu C, Akins RA. 1995. Alternative methods of preparing whole-cell DNA from fungi for dot-blot, restriction analysis, and colony filter hybridization. Analytical biochemistry 225:94-100.
17. Arganoza MT, Akins RA. 1995. A modified colony-filter-hybridization protocol for filamentous fungi. Trends in genetics : TIG 11:381-382.
18. Arganoza MT, Akins RA. 1995. Recombinant mitochondrial plasmids in Neurospora composed of Varkud and a new multimeric mitochondrial plasmid. Current genetics 29:34-43.
19. Arganoza MT, Ohrnberger J, Min J, Akins RA. 1994. Suppressor mutants of Neurospora crassa that tolerate allelic differences at single or at multiple heterokaryon incompatibility loci. Genetics 137:731-742.
20. Arganoza MT, Min J, Hu Z, Akins RA. 1994. Distribution of seven homology groups of mitochondrial plasmids in Neurospora: evidence for widespread mobility between species in nature. Current genetics 26:62-73.
21. Nargang FE, Pande S, Kennell JC, Akins RA, Lambowitz AM. 1992. Evidence that a 1.6 kilobase region of Neurospora mtDNA was derived by insertion of part of the LaBelle mitochondrial plasmid. Nucleic acids research 20:1101-1108.
22. Guo QB, Akins RA, Garriga G, Lambowitz AM. 1991. Structural analysis of the Neurospora mitochondrial large rRNA intron and construction of a mini-intron that shows protein-dependent splicing. The Journal of biological chemistry 266:1809-1819.
23. Kubelik AR, Kennell JC, Akins RA, Lambowitz AM. 1990. Identification of Neurospora mitochondrial promoters and analysis of synthesis of the mitochondrial small rRNA in wild-type and the promoter mutant [poky]. The Journal of biological chemistry 265:4515-4526.
24. Cherniack AD, Garriga G, Kittle JD, Jr., Akins RA, Lambowitz AM. 1990. Function of Neurospora mitochondrial tyrosyl-tRNA synthetase in RNA splicing requires an idiosyncratic domain not found in other synthetases. Cell 62:745-755.
25. Akins RA, Lambowitz AM. 1990. Analysis of large deletions in the Mauriceville and Varkud mitochondrial plasmids of Neurospora. Current genetics 18:365-369.
26. Majumder AL, Akins RA, Wilkinson JG, Kelley RL, Snook AJ, Lambowitz AM. 1989. Involvement of tyrosyl-tRNA synthetase in splicing of group I introns in Neurospora crassa mitochondria: biochemical and immunochemical analyses of splicing activity. Molecular and cellular biology 9:2089-2104.
27. Akins RA, Kelley RL, Lambowitz AM. 1989. Characterization of mutant mitochondrial plasmids of Neurospora spp. that have incorporated tRNAs by reverse transcription. Molecular and cellular biology 9:678-691.
28. Mann BJ, Akins RA, Lambowitz AM, Metzenberg RL. 1988. The structural gene for a phosphorus-repressible phosphate permease in Neurospora crassa can complement a mutation in positive regulatory gene nuc-1. Molecular and cellular biology 8:1376-1379.
29. Kuiper MT, Akins RA, Holtrop M, de Vries H, Lambowitz AM. 1988. Isolation and analysis of the Neurospora crassa Cyt-21 gene. A nuclear gene encoding a mitochondrial ribosomal protein. The Journal of biological chemistry 263:2840-2847.
30. Akins RA, Grant DM, Stohl LL, Bottorff DA, Nargang FE, Lambowitz AM. 1988. Nucleotide sequence of the Varkud mitochondrial plasmid of Neurospora and synthesis of a hybrid transcript with a 5' leader derived from mitochondrial RNA. Journal of molecular biology 204:1-25.
31. Paietta JV, Akins RA, Lambowitz AM, Marzluf GA. 1987. Molecular cloning and characterization of the cys-3 regulatory gene of Neurospora crassa. Molecular and cellular biology 7:2506-2511.
32. Akins RA, Lambowitz AM. 1987. A protein required for splicing group I introns in Neurospora mitochondria is mitochondrial tyrosyl-tRNA synthetase or a derivative thereof. Cell 50:331-345.
33. Lambowitz AM, Akins RA, Kelley RL, Pande S, Nargang FE. 1986. Mitochondrial plasmids of Neurospora and other filamentous fungi. Basic life sciences 40:83-92.
34. Akins RA, Kelley RL, Lambowitz AM. 1986. Mitochondrial plasmids of Neurospora: integration into mitochondrial DNA and evidence for reverse transcription in mitochondria. Cell 47:505-516.
35. Akins RA, Lambowitz AM. 1985. General method for cloning Neurospora crassa nuclear genes by complementation of mutants. Molecular and cellular biology 5:2272-2278.
36. Stohl LL, Akins RA, Lambowitz AM. 1984. Characterization of deletion derivatives of an autonomously replicating Neurospora plasmid. Nucleic acids research 12:6169-6178.
37. Akins RA, Lambowitz AM. 1984. The [poky] mutant of Neurospora contains a 4-base-pair deletion at the 5' end of the mitochondrial small rRNA. Proceedings of the National Academy of Sciences of the United States of America 81:3791-3795.
38. Byers TJ, Akins RA, Maynard BJ, Lefken RA, Martin SM. 1980. Rapid growth of Acanthamoeba in defined media; induction of encystment by glucose-acetate starvation. The Journal of protozoology 27:216-219.
39. Akins RA, Byers TJ. 1980. Differentiation promoting factors induced in Acanthamoeba by inhibitors of mitochondrial macromolecule synthesis. Developmental biology 78:126-140.