Adrian Olivares, Ph.D.

Assistant Professor

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Faculty Appointments
Assistant Professor of Biochemistry
Ph.D., Yale University, New Haven, ConnecticutB.Sc., Baylor University, Waco, Texas
Office Address
639D Light Hall
2215 Garland Ave
Nashville, TN 37232
Research Description
Nuclear positioning, force sensing, and disease.

During the course of a cell’s life, the nucleus constantly moves; it is repositioned in motile cells and during differentiation. Moreover, mechanical signals originating outside the cell are carried to the nucleus to regulate gene transcription in a process known as mechanotransduction. Mutations in genes associated with proper nuclear positioning and mechanotransduction trigger apoptosis and lead to human disease, including lisencephaly, cardiomyopathies, and muscular dystrophies. Years of cell biological and, more recently, structural and biochemical studies provide clear evidence that cell adhesion molecules (CAMs) at the plasma membrane carry mechanical signals from outside the cell to the underlying cytoskeleton surrounding the nucleus. These signals are transmitted across the nuclear envelope (NE) to the nucleoskeleton within the nucleus. How CAMs and the cytoskeleton sense and transmit mechanical force has been well studied in vivo and in vitro but relatively little mechanistic detail is known about the nuclear components involved in this network. Recent studies show that protein complexes, which span the nuclear envelope, directly connect the cytoskeleton to the nucleoskeleton and likely serve as force-transducing modules for nuclear positioning and mechanotransduction. Because the molecular mechanisms underlying nuclear force sensing are not well understood, my laboratory is studying how these LINC (linker of nucleoskeleton and cytoskeleton) complexes transmit force across the nuclear envelope to position the nucleus and regulate gene expression.
Research Keywords
Mechanochemistry of force transduction across the nuclear envelope
Olivares AO, Baker TA, Sauer RT. Mechanical Protein Unfolding and Degradation. Annu. Rev. Physiol. 2018 Feb 2/10/2018; 80: 413-29. PMID: 29433415, DOI: 10.1146/annurev-physiol-021317-121303, ISSN: 1545-1585.

Olivares AO, Kotamarthi HC, Stein BJ, Sauer RT, Baker TA. Effect of directional pulling on mechanical protein degradation by ATP-dependent proteolytic machines. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2017 Jul 7/19/2017; PMID: 28724722, PII: 1707794114, DOI: 10.1073/pnas.1707794114, ISSN: 1091-6490.

Cordova JC, Olivares AO, Lang MJ. Mechanically Watching the ClpXP Proteolytic Machinery. Methods Mol. Biol. 2017; 1486: 317-41. PMID: 27844434, DOI: 10.1007/978-1-4939-6421-5_12, ISSN: 1940-6029.

Olivares AO, Baker TA, Sauer RT. Mechanistic insights into bacterial AAA+ proteases and protein-remodelling machines. Nat. Rev. Microbiol [print-electronic]. 2016 Jan; 14(1): 33-44. PMID: 26639779, PII: nrmicro.2015.4, DOI: 10.1038/nrmicro.2015.4, ISSN: 1740-1534.

Iosefson O, Olivares AO, Baker TA, Sauer RT. Dissection of Axial-Pore Loop Function during Unfolding and Translocation by a AAA+ Proteolytic Machine. Cell Rep [print-electronic]. 2015 Aug 8/11/2015; 12(6): 1032-41. PMID: 26235618, PMCID: PMC4536184, PII: S2211-1247(15)00733-0, DOI: 10.1016/j.celrep.2015.07.007, ISSN: 2211-1247.

Olivares AO, Nager AR, Iosefson O, Sauer RT, Baker TA. Mechanochemical basis of protein degradation by a double-ring AAA+ machine. Nat. Struct. Mol. Biol [print-electronic]. 2014 Oct; 21(10): 871-5. PMID: 25195048, PMCID: PMC4190165, PII: nsmb.2885, DOI: 10.1038/nsmb.2885, ISSN: 1545-9985.

Cordova JC, Olivares AO, Shin Y, Stinson BM, Calmat S, Schmitz KR, Aubin-Tam ME, Baker TA, Lang MJ, Sauer RT. Stochastic but highly coordinated protein unfolding and translocation by the ClpXP proteolytic machine. Cell. 2014 Jul 7/31/2014; 158(3): 647-58. PMID: 25083874, PMCID: PMC4134808, PII: S0092-8674(14)00800-9, DOI: 10.1016/j.cell.2014.05.043, ISSN: 1097-4172.

Aubin-Tam ME, Olivares AO, Sauer RT, Baker TA, Lang MJ. Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine. Cell. 2011 Apr 4/15/2011; 145(2): 257-67. PMID: 21496645, PMCID: PMC3108460, PII: S0092-8674(11)00313-8, DOI: 10.1016/j.cell.2011.03.036, ISSN: 1097-4172.

Islam K, Chin HF, Olivares AO, Saunders LP, De La Cruz EM, Kapoor TM. A myosin V inhibitor based on privileged chemical scaffolds. Angew. Chem. Int. Ed. Engl. 2010 Nov 11/2/2010; 49(45): 8484-8. PMID: 20878825, PMCID: PMC3063097, DOI: 10.1002/anie.201004026, ISSN: 1521-3773.

Oguchi Y, Mikhailenko SV, Ohki T, Olivares AO, De La Cruz EM, Ishiwata S. Robust processivity of myosin V under off-axis loads. Nat. Chem. Biol [print-electronic]. 2010 Apr; 6(4): 300-5. PMID: 20228794, PMCID: PMC2917589, PII: nchembio.322, DOI: 10.1038/nchembio.322, ISSN: 1552-4469.

Prochniewicz E, Chin HF, Henn A, Hannemann DE, Olivares AO, Thomas DD, De La Cruz EM. Myosin isoform determines the conformational dynamics and cooperativity of actin filaments in the strongly bound actomyosin complex. J. Mol. Biol [print-electronic]. 2010 Feb 2/26/2010; 396(3): 501-9. PMID: 19962990, PMCID: PMC2834967, PII: S0022-2836(09)01457-0, DOI: 10.1016/j.jmb.2009.11.063, ISSN: 1089-8638.

De La Cruz EM, Olivares AO. Watching the walk: observing chemo-mechanical coupling in a processive myosin motor. HFSP J [print-electronic]. 2009; 3(2): 67-70. PMID: 19794813, PMCID: PMC2707789, DOI: 10.2976/1.3095425, ISSN: 1955-2068.

Altieri SL, Clayton GM, Silverman WR, Olivares AO, De la Cruz EM, Thomas LR, Morais-Cabral JH. Structural and energetic analysis of activation by a cyclic nucleotide binding domain. J. Mol. Biol [print-electronic]. 2008 Sep 9/5/2008; 381(3): 655-69. PMID: 18619611, PMCID: PMC2555981, PII: S0022-2836(08)00698-0, DOI: 10.1016/j.jmb.2008.06.011, ISSN: 1089-8638.

Oguchi Y, Mikhailenko SV, Ohki T, Olivares AO, De La Cruz EM, Ishiwata S. Load-dependent ADP binding to myosins V and VI: implications for subunit coordination and function. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Jun 6/3/2008; 105(22): 7714-9. PMID: 18509050, PMCID: PMC2409399, PII: 0800564105, DOI: 10.1073/pnas.0800564105, ISSN: 1091-6490.

Au JK, Olivares AO, Henn A, Cao W, Safer D, De La Cruz EM. Widely distributed residues in thymosin beta4 are critical for actin binding. Biochemistry [print-electronic]. 2008 Apr 4/1/2008; 47(13): 4181-8. PMID: 18327913, PMCID: PMC2587058, DOI: 10.1021/bi701769u, ISSN: 0006-2960.

Mikhailenko SV, Oguchi Y, Ohki T, Shimozawa T, Olivares AO, De La Cruz EM, Ishiwata S. How the Load and the Nucleotide State Affect the Actin Filament Binding Mode of the Molecular Motor Myosin V. J Korean Phys Soc. 2008; 53(3): 1726-30. PMID: 20552037, PMCID: PMC2884403, ISSN: 0374-4884.

Olivares AO, Chang W, Mooseker MS, Hackney DD, De La Cruz EM. The tail domain of myosin Va modulates actin binding to one head. J. Biol. Chem [print-electronic]. 2006 Oct 10/20/2006; 281(42): 31326-36. PMID: 16921171, PII: M603898200, DOI: 10.1074/jbc.M603898200, ISSN: 0021-9258.

Olivares AO, De La Cruz EM. Holding the reins on myosin V. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Sep 9/27/2005; 102(39): 13719-20. PMID: 16172373, PMCID: PMC1236595, PII: 0507068102, DOI: 10.1073/pnas.0507068102, ISSN: 0027-8424.

Hannemann DE, Cao W, Olivares AO, Robblee JP, De La Cruz EM. Magnesium, ADP, and actin binding linkage of myosin V: evidence for multiple myosin V-ADP and actomyosin V-ADP states. Biochemistry. 2005 Jun 6/21/2005; 44(24): 8826-40. PMID: 15952789, DOI: 10.1021/bi0473509, ISSN: 0006-2960.

Robblee JP, Olivares AO, de la Cruz EM. Mechanism of nucleotide binding to actomyosin VI: evidence for allosteric head-head communication. J. Biol. Chem [print-electronic]. 2004 Sep 9/10/2004; 279(37): 38608-17. PMID: 15247304, PII: M403504200, DOI: 10.1074/jbc.M403504200, ISSN: 0021-9258.

Uemura S, Higuchi H, Olivares AO, De La Cruz EM, Ishiwata S. Mechanochemical coupling of two substeps in a single myosin V motor. Nat. Struct. Mol. Biol [print-electronic]. 2004 Sep; 11(9): 877-83. PMID: 15286720, PII: nsmb806, DOI: 10.1038/nsmb806, ISSN: 1545-9993.

Hadimani MB, Hua J, Jonklaas MD, Kessler RJ, Sheng Y, Olivares A, Tanpure RP, Weiser A, Zhang J, Edvardsen K, Kane RR, Pinney KG. Synthesis, in vitro, and in vivo evaluation of phosphate ester derivatives of combretastatin A-4. Bioorg. Med. Chem. Lett. 2003 May 5/5/2003; 13(9): 1505-8. PMID: 12699742, PII: S0960894X03002063, ISSN: 0960-894X.

Available Postdoctoral Position Details
Posted: 10/21/2016

Postdoctoral position in understanding the mechanochemistry of force transduction across the nuclear envelope

A postdoctoral position is available in my laboratory. You will be joining a new research group with primary research interests in understanding how mechanical forces are transmitted across the nuclear envelope. My laboratory uses a combination of single molecule force spectroscopic and solution biochemical methods to dissect the molecular interactions governing LINC complex assembly/disassembly and force transduction. Candidates should hold a Ph.D. in biochemistry, molecular biology, biophysics, or any related field. Excellent writing and communication skills in English are required. Interested candidates should prepare a single PDF containing a cover letter describing your previous research and explaining your interest in the lab in addition to a CV with contact information of 3 references.

See for more details.